O r i g i n a l R e p o r t Human platelet antigen allelic diversity in Peninsular

W.U.W. Syafawati, Z. Zefarina, Z. Zafarina, M.N. Hassan, M.N. Norazmi, S. Panneerchelvam, G.K. Chambers, and H.A. Edinur

Human platelet antigens (HPAs) are polymorphic and each one containing six subgroups (Department of immunogenic glycoproteins encoded by biallelic genes on human Affairs, Malaysia: http://www.jakoa.gov.my): (Batek, chromosome 17 (HPA-1 to -4 and HPA-6 to -11), chromosome Jahai, Kensiu, Kintak, Lanoh, and Mendriq), (Semai, 5 (HPA-5), and chromosome 6 (HPA-15) and expressed on the surface of platelets. In the present study, we typed seven HPA Temiar, Semoq Beri, Jahut, Che Wong, and Meh Meri), and loci (HPA-1 to -6 and HPA-15) by polymerase chain reaction Proto- (Orang Kanaq, Kuala, Seletar, Jakun, Semelai, using sequence-specific primer and sequence-based typing in 166 and Temuan). blood samples representing three Orang Asli groups (Semang, Senoi, and Proto-Malays) that inhabit . The Semang inhabit northern parts of Peninsular Malaysia Combined with previous HPA data collected for Malay subethnic and are physically of small body size with dark skin and frizzy groups, Malays, Chinese, and Indians, our analyses showed high hair. The Semang are hunter-gatherers and numerically genetic diversity in Peninsular Malaysia, which is consistent with the smallest of all the Orang Asli groups. They arrived in multiple settlements of the region by several founding ancestors (Semang, Senoi, and Proto-Malays) in the last 50,000 years. The Peninsular Malaysia about 50,000 years ago and together gene pools of these ancient populations were then further shaped with Australian Aborigines and Papuans17 are associated with by various evolutionary pressures such as repeated founder those earliest modern humans who migrated out of Africa. effects, natural selection, and admixture with the relatively The Senoi, who inhabit the foothills and lowlands of northern recent arrivals such as Chinese, Indians, and Malay subethnic groups. Medical consequences of this genetic complexity are and central regions of Peninsular Malaysia, are estimated to also discussed, including the risks of platelet alloimmunization have arrived about 8,000 years ago and are the largest group of associated with random platelet transfusion and gestation. Orang Asli. The light-skinned and relatively tall Senoi people Immunohematology 2016;32:143–160. are linked to Austro-Asiatic agriculturists who originated from mainland Southeast Asia or South China. In contrast, Proto- Key Words: human platelet antigen, Orang Asli, Semang, Malays arrived quite recently in Peninsular Malaysia (~4,000 Senoi, Proto-Malays, Peninsular Malaysia years ago).18 They are believed to be descendants of Neolithic Austronesian voyagers who migrated out of Taiwan to islands Human platelet antigens (HPAs) are expressed on the of Southeast Asia, and Near and Remote Oceania.19 It is from surface of platelets. They are polymorphic and immunogenic this Orang Asli group that the admixed Deutero-Malays later glycoproteins encoded by the biallelic genes on human emerged. Their contemporary gene pool now contains recent chromosomes 17 (HPA-1 to -4 and HPA-6 to -11), 5 (HPA-5), minor admixture from other residents in Malaysia, including and 6 (HPA-15).1,2 HPAs are clinically relevant in transfusion Chinese and Indians.20 and gestation, since incompatibility can cause posttransfusion Overall, our present study on HPA in representative OA purpura (PTP),3 platelet transfusion refractoriness (PTR),4 groups/subgroups complements earlier studies on Malays,16 and neonatal alloimmune thrombocytopenia (NAIT).5 Chinese,16 Indians,16 and Malay subethnic groups15 and thus Collections of HPA data have been reported for many provides more fully extensive documentation of HPA allelic populations, including Europeans,6–8 Asians,9–13 Africans,1 spectra in Peninsular Malaysia for the first time. These data and Amerindians.14 Knowledge about local distributions of sets can now be subjected to a small-scale meta-analysis HPAs is useful for population and disease studies as well as for study of ancestry and used to estimate the risks of platelet estimating the risk of platelet alloimmunization. In Peninsular alloimmunization associated with random platelet transfusion Malaysia, HPA data have been collected and reported for Malay and gestation. We present the findings from this investigation subethnic groups,15 Malays,16 Chinese,16 and Indians,16 but and our comments on their significance. not for the minority indigenous peoples collectively known as Orang Asli. They are represented by three major groups with

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Materials and Methods samples using specific discriminating oligonucleotide primers (forward: 5´-GAATATGGATCAATATGCAGTA-3´; reverse: Blood Samples 5´-AAAAGACAAAGCCAAGGA-3´) and PCR cycling condi- A total of 166 blood samples were obtained with informed tions reported by Xu et al.21 The amplified PCR products were consent from all three Orang Asli groups: Semang (Batek: then purified (QIAquick PCR Purification, QIAGEN) and N = 27, Che Wong: N = 26, and Kensiu: N = 36), Senoi (Lanoh: analyzed using agarose gel electrophoresis. The remaining N = 25 and Semai: N = 41), and Proto-Malays (Orang Kanaq: aliquots of purified PCR amplicons were sent to the DNA N = 11). The Orang Asli study samples were then split into sequencing service provided by 1st BASE Biochemicals, smaller subsamples of unrelated (u) individuals; uBatek , (Applied Biosystems 3730xl DNA analyzer, Foster (N = 17), uChe Wong (N = 14), uKensiu (N = 21), uLanoh (N = City, CA). 13), uSemai (N = 34), and uProto-Malays (N = 7). All volunteers were self-declared as having three generations lacking any Statistical Analyses admixture with other ethnicities. This study was reviewed and Allele and genotype frequencies were determined using approved by the human ethics committee of the University the following formula: Sains Malaysia [reference no. USM/JEPeM/1406217 and USM/PPP/ethics committee/2012(19)]. genotype frequency = number of genotype observed/ number of individuals and allele frequency = DNA Extraction number of allele observed/2 (number of individuals) DNA from blood samples were extracted using a kit (QIAamp DNA Mini Kit, QIAGEN, Hilden, Germany). χ2 tests were used for evaluating Hardy-Weinberg Extractions were performed according to the manufacturer’s equilibrium (HWE) in Orang Asli using the formula: instructions. The eluted DNA was quantified by spectrophotometry (NanoDrop 2000c Spectrophotometer, χ2 = ∑ [(O – E) 2/E] Thermo Scientific, Waltham, MA) and stored at –20°C until further use. where O and E are observed and expected number of genotypes, respectively. Significant departure from HWE is considered Sequence-Specific Primer Genotyping of HPA-1 to -6 at a p value <0.05.22 Genetic differentiation between pairs of and HPA-15 Loci Orang Asli subgroups and between Orang Asli and previously The polymerase chain reaction using sequence- studied Malay subethnic groups,15 Malays,16 Chinese,16 and specific primer (PCR-SSP) genotyping protocols, including Indians16 were evaluated using Fischer’s exact test in a software oligonucleotide primers and thermal cycling parameters, program (SPSS, SPSS Inc., Chicago, IL). Two data sets were reported by Kupatawintu et al.11 and Feng et al.,12 were used considered significantly different at pa value <0.05. Genetic to genotype HPA-1, -2, -4, -5, and -15, and HPA-3 and -6, relationships between Orang Asli subgroups, Malay subethnic respectively. The amplified products and DNA size markers groups, and other reference populations were studied were separated by using stained 2 percent agarose gels (SYBR using principal coordinate analysis software (Multivariate Safe, Life Technologies Corp., Singapore) and visualized using Statistical Software Package 3, Kovach Computing Services, a digital gel documentation system (Vilber Lourmat Software, Pentraeth, Isle of Anglesey, UK). The HPA frequency data VILBER, Eberhardzell, Germany). All HPA allelic scoring was for reference populations were obtained from published made by comparing band patterns for amplified HPA allele- resources6–9,13,15,16,23,24 and the IPD-HPA database.1 The specific products with a DNA size standard. probability of transfusion and pregnancy alloimmunization were calculated using the formula established by De La Vega Sequence-Based Typing of HPA-15 Elena et al.14 Our PCR-SSP typing showed an extremely high frequency of HPA-15b/b genotype in Orang Asli. Indeed, the HPA- Results 15b allele is fixed in Batek. Thus, we randomly selected 20 samples and genotyped the HPA-15 locus using sequence- The HPA genotype data for Orang Asli and their smaller based typing (SBT) as part of our verification procedure. subsamples of unrelated (u) individuals are shown in Tables 1 The HPA-15 locus was amplified from these selected DNA and 2, respectively. No significant departures from HWE were

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Table 1. HPA genotype profiles and Hardy-Weinberg equilibrium estimations for Orang Asli subgroups

Batek (N = 27) Che Wong (N = 26) Kensiu (N = 36) Lanoh (N = 25) Semai (N = 40) Orang Kanaq (N = 11) HPA O E p O E p O E p O E p O E p O E p 1a/1a 1.000 1.000 NA 1.000 1.000 NA 0.917 0.918 0.794 1.000 1.000 NA 0.976 0.976 0.937 1.000 1.000 NA 1a/1b 0.000 0.000 0.000 0.000 0.083 0.080 0.000 0.000 0.024 0.024 0.000 0.000 1b/1b 0.000 0.000 0.000 0.000 0.000 0.002 0.000 0.000 0.000 0.001 0.000 0.000 2a/2a 1.000 1.000 NA 1.000 1.000 NA 1.000 1.000 NA 1.000 1.000 NA 1.000 1.000 NA 1.000 1.000 NA 2a/2b 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 2b/2b 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 3a/3a 0.185 0.250 0.178 0.115 0.179 0.184 0.750 0.766 0.391 0.480 0.410 0.127 0.463 0.45 0.695 0.636 0.669 0.461 3a/3b 0.630 0.500 0.615 0.488 0.250 0.219 0.320 0.461 0.415 0.442 0.364 0.298 3b/3b 0.185 0.250 0.270 0.333 0.000 0.015 0.200 0.130 0.122 0.108 0.000 0.033 4a/4a 1.000 1.000 NA 1.000 1.000 NA 1.000 1.000 NA 1.000 1.000 NA 1.000 1.000 NA 1.000 1.000 NA 4a/4b 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 4b/4b 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 5a/5a 0.704 0.726 0.366 0.615 0.622 0.848 0.694 0.718 0.279 1.000 1.000 NA 0.781 0.793 0.430 1.000 1.000 NA 5a/5b 0.296 0.252 0.346 0.333 0.306 0.259 0.000 0.000 0.220 0.195 0.000 0.000 5b/5b 0.000 0.022 0.039 0.045 0.000 0.023 0.000 0.000 0.000 0.012 0.000 0.000 6a/6a 1.000 1.000 NA 1.000 1.000 NA 1.000 1.000 NA 1.000 1.000 NA 1.000 1.000 NA 1.000 1.000 NA 6a/6b 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 6b/6b 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 15a/15a 0.000 0.000 NA 0.077 0.250 <0.001 0.083 0.130 0.221 0.080 0.068 0.747 0.342 0.275 0.088 0.818 0.826 0.740 15a/15b 0.000 0.000 0.846 0.500 0.556 0.461 0.360 0.385 0.366 0.499 0.182 0.165 15b/15b 1.000 1.000 0.077 0.250 0.361 0.408 0.560 0.548 0.293 0.226 0.000 0.008 HPA = human platelet antigen; O = observed frequency; E = expected frequency; NA = not applicable. observed, except for HPA-15 in Che Wong. The frequencies widely scattered in the top left and right parts of the principal of the major (most common) HPA alleles in Orang Asli coordinate (PCO) plot (Fig. 1). In contrast, other populations subgroups were as follows: HPA-1a (0.958–1.000), -2a (1.000), such as Taiwan aborigines and Europeans are plotted on the -4a (1.000), -5a (0.788–1.000), and -6a (1.000), as shown in center and top right-hand corner of Figure 1, respectively. Tables 3 and 4. There are marked differences, however, for HPA-3 and -15 allelic distributions in Orang Asli. For instance, Discussion HPA-3b is found at relatively high frequency in Batek (0.500) and Che Wong (0.577), whereas HPA-3a was recorded as A series of immigrations have contributed to today’s the most frequent HPA-3 type in Kensiu, Lanoh, Senoi, and highly diverse and complex genetic structure in Peninsular Orang Kanaq (0.640–0.875). For the HPA-15 locus, HPA- Malaysia. Therefore, genetic screening of medically important 15b was the most frequent allele in Batek, Kensiu, and Lanoh, regions within the human genome should become a primary compared with HPA-15a in Orang Kanaq and Semai. The target of biomedical research to better promote the delivery Che Wong showed an equal frequency of HPA-15a and -15b of equitable healthcare to communities. In the present study, alleles. Exact tests for population differentiation showed no we screened the HPA-1 to -6 and HPA-15 loci in the following significant differences between pairs of Orang Asli subgroups OA subgroups; Batek, Che Wong, Kensiu, Lanoh, Semai, and and their smaller subsample of unrelated individuals (Table 5). Orang Kanaq, who represent three larger Orang Asli groups Therefore, we used the larger combined (related and unrelated presently living in Peninsular Malaysia. individuals) set of HPA data for Orang Asli to compare them The HPA data collected for the Orang Asli subgroups with that reported for Malay subethnic groups,15 Malays,16 generally showed similarities in terms of their most frequently Chinese,16 and Indians16 (Table 6). Our results show significant observed genotypes and alleles (Tables 1 and 3). The only differences between some of the HPA data sets listed in Table 6, exceptions are the HPA-3 and -15 systems, where significant especially for HPA-3 and -15. The Malaysia subpopulations differences were not only recorded between Orang Asli including Orang Asli, Malays, Chinese, and Indians are groups (Semang versus Senoi versus Proto-Malays), but also

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Fig. 1. Principal coordinate plot showing genetic relationships between the studied Orang Asli subgroups and other reference populations. The plot was constructed using HPA-1 to -5 allele frequencies from the reference populations listed in Table 3.

Table 2. HPA genotype profiles and Hardy-Weinberg equilibrium estimations for smaller subsamples of unrelated Orang Asli individuals

uBatek (N = 17) uChe Wong (N = 14) uKensiu (N = 21) uLanoh (N = 13) uSemai (N = 34) uOrang Kanaq (N = 7) HPA O E p O E p O E p O E p O E p O E p 1a/1a 1.000 1.000 NA 1.000 1.000 NA 0.857 0.862 0.725 1.000 1.000 NA 0.971 0.971 0.931 1.000 1.000 NA 1a/1b 0.000 0.000 0.000 0.000 0.143 0.133 0.000 0.000 0.029 0.029 0.000 0.000 1b/1b 0.000 0.000 0.000 0.000 0.000 0.005 0.000 0.000 0.000 0.000 0.000 0.000 2a/2a 1.000 1.000 NA 1.000 1.000 NA 1.000 1.000 NA 1.000 1.000 NA 1.000 1.000 NA 1.000 1.000 NA 2a/2b 0.000 0.000 0.000 0.000 0.000 0.000 0.000 1.000 0.000 0.000 0.000 0.000 2b/2b 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 3a/3a 0.118 0.222 0.086 0.143 0.154 0.857 0.810 0.819 0.630 0.462 0.379 0.207 0.471 0.438 0.395 0.714 0.735 0.659 3a/3b 0.706 0.498 0.500 0.477 0.191 0.172 0.308 0.473 0.382 0.448 0.286 0.245 3b/3b 0.177 0.28 0.357 0.369 0.000 0.009 0.231 0.148 0.147 0.114 0.000 0.020 4a/4a 1.000 1.000 NA 1.000 1.000 NA 1.000 1.000 NA 1.000 1.000 NA 1.000 1.000 NA 1.000 1.000 NA 4a/4b 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 4b/4b 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 5a/5a 0.765 0.779 0.583 0.643 0.617 0.571 0.667 0.694 0.359 1.000 1.000 NA 0.794 0.831 0.573 1.000 1.000 NA 5a/5b 0.235 0.208 0.286 0.337 0.333 0.278 0.000 0.000 0.206 0.161 0.000 0.000 5b/5b 0.000 0.014 0.071 0.046 0.000 0.030 0.000 0.000 0.000 0.080 0.000 0.000 6a/6a 1.000 1.000 NA 1.000 1.000 NA 1.000 1.000 NA 1.000 1.000 NA 1.000 1.000 NA 1.000 1.000 NA 6a/6b 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 6b/6b 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 15a/15a 0.000 0.000 NA 0.070 0.250 0.008 0.095 0.128 0.519 0.077 0.053 0.500 0.294 0.236 0.171 0.857 0.862 0.839 15a/15b 0.000 0.000 0.857 0.500 0.524 0.459 0.231 0.355 0.382 0.500 0.143 0.133 15b/15b 1.000 1.000 0.070 0.250 0.381 0.413 0.692 0.592 0.324 0.265 0.000 0.005 HPA = human platelet antigen; u = unrelated; O = observed frequency; E = expected frequency; NA = not applicable.

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between Semang subgroups (Batek versus Kensiu for HPA-3 differentiation within Orang Asli subgroups (specifically, and Batek versus Che Wong for HPA-15; Table 6). A similar between Semang subgroups) and between Proto-Malays and observation was also apparent between Proto-Malays and their Malay subethnic groups has also been reported by others.25 Austronesian relatives, the Malay subethnic groups (Table 6). In contrast, there are no obvious differences between the two These genetic differences are all well demonstrated on the Senoi subgroups (Lanoh and Semai) who are members of the PCO plot constructed using HPA-1 to -5 allele frequencies largest Orang Asli group in Peninsular Malaysia (Table 6 and (Fig. 1). The PCO analysis converts genetic variations Fig. 1). This finding might be attributable to the relatively small between HPA data sets into several axes and the distance sizes of the Semang and Proto-Malay populations. As such, between populations demonstrates their genetic relationship. they are expected to be much more likely affected by selective The two most informative axes were selected to construct forces and bottlenecks as compared with the larger Orang Asli the two-dimentional scatter plot shown in Figure 1. Genetic group, the Senoi, or with other Malaysian subpopulations,

Table 3. HPA allele frequencies in Orang Asli subgroups and other reference populations

Population 1a 1b 2a 2b 3a 3b 4a 4b 5a 5b 6a 6b 15a 15b Batek 1.000 0.000 1.000 0.000 0.500 0.500 1.000 0.000 0.852 0.148 1.000 0.000 0.000 1.000 Che Wong 1.000 0.000 1.000 0.000 0.423 0.577 1.000 0.000 0.788 0.212 1.000 0.000 0.500 0.500 Kensiu 0.958 0.042 1.000 0.000 0.875 0.125 1.000 0.000 0.847 0.153 1.000 0.000 0.361 0.639 Lanoh 1.000 0.000 1.000 0.000 0.640 0.360 1.000 0.000 1.000 0.000 1.000 0.000 0.260 0.740 Semai 0.988 0.012 1.000 0.000 0.671 0.329 1.000 0.000 0.890 0.110 1.000 0.000 0.524 0.476 Orang Kanaq 1.000 0.000 1.000 0.000 0.818 0.182 1.000 0.000 1.000 0.000 1.000 0.000 0.909 0.091 Champa15 0.980 0.020 0.970 0.030 0.677 0.323 1.000 0.000 0.990 0.010 0.980 0.020 0.480 0.520 Kelantan15 1.000 0.000 0.940 0.060 0.571 0.429 1.000 0.000 1.000 0.000 0.990 0.010 0.490 0.510 Banjar15 1.000 0.000 0.950 0.050 0.616 0.384 0.950 0.050 0.950 0.050 0.980 0.020 0.480 0.520 Bugis15 1.000 0.000 1.000 0.000 0.554 0.446 1.000 0.000 0.950 0.050 0.910 0.090 0.620 0.380 Jawa15 1.000 0.000 1.000 0.000 0.628 0.372 1.000 0.000 0.960 0.040 1.000 0.000 0.450 0.550 Malays16 0.975 0.025 0.963 0.037 0.503 0.497 0.995 0.005 0.950 0.050 0.993 0.007 0.515 0.485 Chinese16 1.000 0.000 0.967 0.033 0.573 0.427 0.998 0.002 0.983 0.017 0.983 0.017 0.498 0.502 Indians16 0.885 0.115 0.960 0.040 0.620 0.380 0.995 0.005 0.940 0.060 0.995 0.005 0.408 0.592 Kinh Vietnam23 0.986 0.014 0.953 0.047 0.486 0.514 1.000 0.000 0.972 0.028 0.986 0.014 0.523 0.477 Australian Aboriginal7 0.997 0.003 1.000 0.000 0.932 0.068 1.000 0.000 0.754 0.246 NA NA NA NA Chinese Han13 0.994 0.006 0.952 0.048 0.595 0.405 0.995 0.005 0.986 0.014 0.987 0.013 0.532 0.468 Minnan9 0.998 0.002 0.957 0.043 0.550 0.450 0.995 0.005 0.990 0.010 NA NA NA NA Hakka9 1.000 0.000 0.970 0.030 0.602 0.398 0.996 0.004 0.996 0.004 NA NA NA NA Atayal9 1.000 0.000 0.930 0.070 0.500 0.500 1.000 0.000 1.000 0.000 NA NA NA NA Saisiat9 1.000 0.000 0.956 0.044 0.456 0.544 1.000 0.000 0.965 0.035 NA NA NA NA Bunun9 1.000 0.000 0.989 0.011 0.417 0.583 1.000 0.000 1.000 0.000 NA NA NA NA Tsou9 1.000 0.000 1.000 0.000 0.245 0.755 1.000 0.000 0.980 0.020 NA NA NA NA Rukai9 1.000 0.000 0.970 0.030 0.570 0.430 1.000 0.000 1.000 0.000 NA NA NA NA Paiwan9 1.000 0.000 1.000 0.000 0.667 0.333 1.000 0.000 1.000 0.000 NA NA NA NA Ami9 1.000 0.000 0.995 0.005 0.495 0.505 1.000 0.000 0.975 0.026 NA NA NA NA Yami 9 1.000 0.000 1.000 0.000 0.566 0.434 1.000 0.000 0.984 0.016 NA NA NA NA Pazeh9 1.000 0.000 0.960 0.040 0.610 0.390 0.990 0.010 0.980 0.020 NA NA NA NA Maori24 0.968 0.032 0.947 0.053 0.564 0.436 1.000 0.000 1.000 0.000 1.000 0.000 0.362 0.638 Polynesian24 0.980 0.020 0.920 0.080 0.720 0.280 1.000 0.000 0.940 0.060 0.900 0.100 0.300 0.700 Wales8 0.825 0.175 0.902 0.098 0.607 0.393 1.000 0.000 0.903 0.097 1.000 0.000 NA NA Italy1 0.850 0.150 0.980 0.110 0.610 0.390 1.000 0.000 0.900 0.100 1.000 0.000 NA NA UK6 0.840 0.160 0.925 0.075 0.627 0.373 1.000 0.000 0.914 0.086 1.000 0.000 NA NA Australian7 0.858 0.142 0.927 0.073 0.599 0.401 1.000 0.000 0.905 0.095 NA NA NA NA HPA = human platelet antigen; NA = not available.

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Table 4. HPA allele frequencies for the smaller subsamples of unrelated Orang Asli individuals

Population 1a 1b 2a 2b 3a 3b 4a 4b 5a 5b 6a 6b 15a 15b uBatek 1.000 0.000 1.000 0.000 0.471 0.529 1.000 0.000 0.882 0.118 1.000 0.000 0.000 1.000 uChe Wong 1.000 0.000 1.000 0.000 0.393 0.607 1.000 0.000 0.786 0.214 1.000 0.000 0.500 0.500 uKensiu 0.929 0.071 1.000 0.000 0.905 0.095 1.000 0.000 0.833 0.167 1.000 0.000 0.357 0.643 uLanoh 1.000 0.000 1.000 0.000 0.615 0.385 1.000 0.000 1.000 0.000 1.000 0.000 0.231 0.769 uSemai 0.985 0.015 1.000 0.000 0.662 0.338 1.000 0.000 0.912 0.088 1.000 0.000 0.485 0.515 uOrang Kanaq 1.000 0.000 1.000 0.000 0.857 0.143 1.000 0.000 1.000 0.000 1.000 0.000 0.929 0.071 HPA = human platelet antigen; u = unrelated.

Table 5. Homogeneity tests (p values), based on HPA data, between pairs of Orang Asli subgroups and their smaller subsample of unrelated individuals

Batek uBatek Che Wong uChe Wong Kensiu uKensiu Lanoh uLanoh Semai uSemai Orang Kanaq uOrang Kanaq HPA-1 Batek * * * * * * * * * * * * uBatek NA * * * * * * * * * * * Che Wong NA NA * * * * * * * * * * uChe Wong NA NA NA * * * * * * * * * Kensiu NA NA NA NA * * * * * * * * uKensiu 0.533 NA 0.284 0.259 0.250 * * * * * * * Lanoh NA NA NA NA NA 0.284 * * * * * * uLanoh NA NA NA NA NA 0.270 NA * * * * * Semai NA NA NA NA NA 0.551 NA NA * * * * uSemai 1.000 1.000 1.000 1.000 1.000 0.150 1.000 1.000 1.000 * * * Orang Kanaq NA NA NA NA NA 1.000 NA NA NA 1.000 * * uOrang Kanaq NA NA NA NA NA 0.551 NA NA NA 1.000 NA * HPA-3 Batek * * * * * * * * * * * * uBatek 0.623 * * * * * * * * * * * Che Wong 0.578 1.000 * * * * * * * * * * uChe Wong 0.583 0.588 0.440 * * * * * * * * * Kensiu <0.001 0.002 0.006 0.004 * * * * * * * * uKensiu <0.001 <0.001 <0.001 <0.001 0.443 * * * * * * * Lanoh 0.853 0.056 0.065 0.171 0.417 0.032 * * * * * * uLanoh 0.861 0.065 0.084 0.245 0.197 0.034 1.000 * * * * * Semai 0.633 0.044 0.011 0.159 0.376 0.024 0.533 0.324 * * * * uSemai 0.625 0.039 0.013 0.090 0.269 0.028 1.000 0.827 0.619 * * * Orang Kanaq 1.000 0.012 0.003 0.015 0.603 0.234 0.641 0.641 NA 1.000 * * uOrang Kanaq 0.320 0.012 0.004 0.023 1.000 0.622 0.804 0.478 0.592 0.605 0.576 * HPA-5 Batek * * * * * * * * * * * * uBatek 0.415 * * * * * * * * * * * Che Wong 1.000 0.422 * * * * * * * * * * uChe Wong 0.816 0.544 0.832 * * * * * * * * * Kensiu 0.667 1.000 0.448 0.833 * * * * * * * * uKensiu 1.000 0.721 0.716 0.675 0.729 * * * * * * * Lanoh 0.050 0.121 0.050 0.064 0.106 0.050 * * * * * * uLanoh 0.050 0.113 0.050 0.066 0.102 0.050 NA * * * * * Semai 1.000 1.000 0.656 1.000 1.000 1.000 0.123 0.111 * * * * uSemai 0.199 0.714 0.124 0.157 0.702 0.208 0.317 0.167 0.606 * * * Orang Kanaq 0.251 0.546 0.245 0.626 0.530 0.294 NA NA NA 1.000 * * uOrang Kanaq 0.103 0.283 0.106 0.349 0.263 0.141 NA NA 0.462 0.567 NA *

148 IMMUNOHEMATOLOGY, Volume 32, Number 4, 2016 HPA diversity in Peninsular Malaysia

Table 5. Continued. Batek uBatek Che Wong uChe Wong Kensiu uKensiu Lanoh uLanoh Semai uSemai Orang Kanaq uOrang Kanaq HPA-15 Batek * * * * * * * * * * * * uBatek NA * * * * * * * * * * * Che Wong <0.001 <0.001 * * * * * * * * * * uChe Wong <0.001 <0.001 1.000 * * * * * * * * * Kensiu 0.001 <0.001 0.263 0.208 * * * * * * * * uKensiu 0.003 <0.001 0.163 0.099 1.000 * * * * * * * Lanoh 0.007 0.001 <0.001 0.004 0.225 1.000 * * * * * * uLanoh 0.037 0.026 <0.001 0.001 0.050 0.078 0.245 * * * * * Semai 0.001 <0.001 0.029 0.017 0.073 0.109 0.115 0.060 * * * * uSemai 0.001 <0.001 0.034 0.011 0.180 0.215 0.398 0.086 0.456 * * * Orang Kanaq 0.001 <0.001 0.027 0.019 0.017 0.022 0.024 0.036 0.014 0.007 * * uOrang Kanaq <0.001 <0.001 0.002 0.001 0.001 0.001 0.005 0.003 0.034 0.019 1.000 * Only polymorphic HPA systems were subjected to this analysis. HPA = human platelet antigen; u = unrelated; NA = not applicable.

Table 6. Homogeneity tests (p value), based on HPA data, between Orang Asli and other subpopulations in Peninsular Malaysia

Batek Che Wong Kensiu Lanoh Semai Orang Kanaq Banjar* Bugis* Champa* Jawa* Kelantan* Malays** Chinese** HPA-1 Batek — — — — — — — — — — — — — Che Wong NA — — — — — — — — — — — — Kensiu NA NA — — — — — — — — — — — Lanoh NA NA NA — — — — — — — — — — Semai NA NA NA NA — — — — — — — — — Orang Kanaq NA NA NA NA NA — — — — — — — — Banjar* NA NA NA NA NA NA — — — — — — — Bugis* NA NA NA NA NA NA NA — — — — — — Champa* NA NA NA NA NA NA 0.528 0.507 — — — — — Jawa* NA NA NA NA NA NA NA NA 0.503 — — — — Kelantan* NA NA NA NA NA NA NA NA 0.512 NA — — — Malays** NA NA NA NA NA NA NA NA NA NA NA — — Chinese** NA NA NA NA NA NA NA NA NA NA NA NA — Indians** 0.023 0.026 0.149 0.030 0.012 0.207 0.015 0.006 0.010 0.004 0.004 <0.001 <0.001 HPA-2 Batek — — — — — — — — — — — — — Che Wong NA — — — — — — — — — — — — Kensiu NA NA — — — — — — — — — — — Lanoh NA NA NA — — — — — — — — — — Semai NA NA NA NA — — — — — — — — — Orang Kanaq NA NA NA NA NA — — — — — — — — Banjar* NA NA NA NA NA NA — — — — — — — Bugis* NA NA NA NA NA NA 0.085 — — — — — — Champa* 0.016 0.593 0.486 0.604 0.448 0.800 0.199 1.000 — — — — — Jawa* NA NA NA NA NA NA 0.077 NA 1.000 — — — — Kelantan* NA NA NA NA NA NA 0.034 0.051 0.153 0.046 — — — Malays** 0.315 0.328 0.215 0.343 0.174 0.623 NA NA 0.051 NA NA — — Chinese** 0.425 0.439 0.321 0.453 0.274 0.705 0.481 0.343 0.278 0.347 0.362 0.544 — Indians** 0.338 0.352 0.237 0.366 0.194 0.641 0.542 0.270 0.201 0.276 0.422 1.000 0.840

IMMUNOHEMATOLOGY, Volume 32, Number 4, 2016 149 W.U.W. Syafawati et al.

Table 6. Continued.

Batek Che Wong Kensiu Lanoh Semai Orang Kanaq Banjar* Bugis* Champa* Jawa* Kelantan* Malays** Chinese** HPA-3 Batek — — — — — — — — — — — — — Che Wong 0.655 — — — — — — — — — — — — Kensiu <0.001 0.006 — — — — — — — — — — — Lanoh 0.853 0.065 0.417 — — — — — — — — — — Semai 0.633 0.011 0.376 0.533 — — — — — — — — — Orang Kanaq 1.000 0.003 0.603 0.641 0.356 — — — — — — — — Banjar* 0.195 0.055 0.004 0.690 NA 0.235 — — — — — — — Bugis* 0.001 <0.001 0.001 0.284 0.018 0.065 0.015 — — — — — — Champa* 0.016 0.003 0.017 0.895 0.661 0.364 0.643 0.025 — — — — — Jawa* 0.155 0.030 0.005 0.491 0.935 0.279 1.000 0.007 0.625 — — — — Kelantan* 0.454 0.188 <0.001 0.367 0.428 0.096 0.801 0.002 0.181 0.705 — — — Malays** 0.534 0.333 <0.001 0.041 0.014 0.010 0.190 <0.001 0.001 0.093 0.557 — — Chinese** 0.274 0.078 <0.001 0.251 0.241 0.075 0.758 <0.001 0.058 0.659 0.949 0.127 — Indians** 0.114 0.018 <0.001 0.409 0.672 0.180 0.965 <0.001 0.226 0.971 0.726 0.003 0.394 HPA-4 Batek — — — — — — — — — — — — — Che Wong NA — — — — — — — — — — — — Kensiu NA NA — — — — — — — — — — — Lanoh NA NA NA — — — — — — — — — — Semai NA NA NA NA — — — — — — — — — Orang Kanaq NA NA NA NA NA — — — — — — — — Banjar* NA NA NA NA NA NA — — — — — — — Bugis* NA NA NA NA NA NA 0.085 — — — — — — Champa* NA NA NA NA NA NA 0.048 NA — — — — — Jawa* NA NA NA NA NA NA 0.077 NA NA — — — — Kelantan* NA NA NA NA NA NA 0.093 NA NA NA — — — Malays** NA NA NA NA NA NA <0.001 NA NA NA NA — — Chinese** NA NA NA NA NA NA NA NA NA NA NA 0.368 — Indians** NA NA NA NA NA NA NA NA NA NA NA 0.368 NA HPA-5 Batek — — — — — — — — — — — — — Che Wong 1.000 — — — — — — — — — — — — Kensiu 0.667 0.448 — — — — — — — — — — — Lanoh 0.050 0.050 0.106 — — — — — — — — — — Semai 1.000 0.656 1.000 0.123 — — — — — — — — — Orang Kanaq 0.251 0.245 0.530 NA NA — — — — — — — — Banjar* NA 0.038 NA NA NA NA — — — — — — — Bugis* NA 0.028 NA NA NA NA 0.684 — — — — — — Champa* NA <0.001 NA NA NA NA 0.552 0.157 — — — — — Jawa* NA 0.009 NA NA NA NA 0.027 0.221 0.312 — — — — Kelantan* NA <0.001 NA NA NA NA 0.209 0.115 1.000 0.242 — — — Malays** NA <0.001 NA NA NA NA NA NA NA NA NA — — Chinese** NA <0.001 NA NA NA NA NA NA NA NA NA NA — Indians** 0.026 0.001 0.007 0.202 0.296 0.492 0.914 0.910 0.117 0.745 0.107 0.571 0.009

150 IMMUNOHEMATOLOGY, Volume 32, Number 4, 2016 HPA diversity in Peninsular Malaysia

Table 6. Continued.

Batek Che Wong Kensiu Lanoh Semai Orang Kanaq Banjar* Bugis* Champa* Jawa* Kelantan* Malays** Chinese** HPA-6 Batek — — — — — — — — — — — — — Che Wong NA — — — — — — — — — — — — Kensiu NA NA — — — — — — — — — — — Lanoh NA NA NA — — — — — — — — — — Semai NA NA NA NA — — — — — — — — — Orang Kanaq NA NA NA NA NA — — — — — — — — Banjar* NA NA NA NA NA NA — — — — — — — Bugis* NA NA NA NA NA NA 0.120 — — — — — — Champa* NA NA NA NA NA NA 1.000 0.020 — — — — — Jawa* NA NA NA NA NA NA 0.435 0.011 1.000 — — — — Kelantan* NA NA NA NA NA NA 1.000 0.262 0.564 0.220 — — — Malays** NA NA NA NA NA NA NA NA NA NA NA — — Chinese** NA NA NA NA NA NA NA NA NA NA NA NA — Indians** NA NA NA NA NA NA NA NA NA NA NA NA NA HPA-15 Batek — — — — — — — — — — — — — Che Wong <0.001 — — — — — — — — — — — — Kensiu 0.001 0.263 — — — — — — — — — — — Lanoh 0.007 <0.001 0.225 — — — — — — — — — — Semai 0.001 0.029 0.073 0.115 — — — — — — — — — Orang Kanaq 0.001 0.027 0.017 0.024 0.014 — — — — — — — — Banjar* <0.001 <0.001 0.022 0.071 0.686 0.014 — — — — — — — Bugis* <0.001 0.001 0.003 0.002 0.445 0.064 0.264 — — — — — — Champa* <0.001 0.001 0.081 0.058 0.625 0.003 0.602 0.022 — — — — — Jawa* <0.001 0.084 0.476 0.049 0.739 <0.001 0.047 0.027 0.209 — — — — Kelantan* <0.001 0.002 0.014 0.009 0.085 0.028 0.445 0.851 0.558 0.091 — — — Malays** <0.001 0.009 0.042 0.001 0.160 <0.001 0.055 0.078 0.258 0.438 0.269 — — Chinese** <0.001 0.011 0.078 0.003 0.130 <0.001 0.048 0.046 0.257 0.598 0.185 0.870 — Indians** <0.001 0.001 0.304 0.168 0.067 <0.001 0.109 0.002 0.334 0.303 0.040 0.005 0.017 HPA = human platelet antigen. *Data from previous study; NA = not applicable.15 **Data from previous study.16

such as Indians and Malays. All these effects are also well important, since HPAs have been implicated in pathogeneses demonstrated by the reduced genetic diversity in Batek and of NAIT, 26 P T P, 27 and PTR.28 This complexity might create Proto-Malays. The Batek were also observed to be fixed for a real high-risk scenario in Malaysia, as shown by the high HPA-15b and subsequently have the highest frequency for probability of transfusion and gestation alloimmunization, this allele compared with all other populations that we have particularly between pairs of donors or parents from different characterized for the HPA-15 locus (Tables 1 and 3). ethnic backgrounds (relative risk figures are shown in Tables There are obvious genetic similarities and differences 7–20). Study of PTR and NAIT in Malay, Chinese, and between Orang Asli and other major subpopulations in Indian patients showed the predominance of anti-HPA-3a Peninsular Malaysia (Table 6 and Fig. 1); these are expected together with lesser contributions from anti-HPA-1a, -5b, because of the different origins of their founding ancestors.17–20 and -15b detected in patients with NAIT, associated with The genetic complexity in Peninsular Malaysia is medically mild thrombocytopenia.29 Anti-HPA-5b was also reported

IMMUNOHEMATOLOGY, Volume 32, Number 4, 2016 151 W.U.W. Syafawati et al.

Table 7. Hypothetical transfusion and gestation HPA alloimmunization risks between pairs of Batek and other Malaysian subpopulations

HPA Transfusion Gestation B>B/W/K/L/S/O/BA/BU/C/J/KE/M/CH/I B>B/W/K/L/S/O/BA/BU/C/J/KE/M/CH/I 1a 0/0/0.009/0/0.009/0/0/0/0/0/0/0/0/0.013 0/0/0.001/0/0.001/0/0/0/0/0/0/0/0/0.012 1b 0/0/0.075/0/0.039/0/0/0/0.038/0/0/0.047/0/0.172 0/0/0.039/0/0.012/0/0/0/0.019/0/0/0.024/0/0.090 2a 0/0/0/0/0/0/0.003/0/0.001/0/0.003/0.001/0.001/0.002 0/0/0/0/0/0/0.003/0/0.971/0/0.003/0.001/0.001/0.002 2b 0/0/0/0/0/0/0.090/0/0.054/0/0.099/0.068/0.061/0.072 0/0/0/0/0/0/0.045/0/0.029/0/0.051/0.034/0.031/0.037 3a 0.188/0.222/0.016/0.241/0.096/0.032/0.125/0.159/0.093/0.119/0.150/0.186/0.149/0.123 0.125/0.141/0.014/0.083/0.072/0.027/0.091/0.110/0.070/0.087/0.105/0.124/0.104/0.089 3b 0.188/0.147/0.179/0.241/0.248/0.221/0.235/0.213/0.248/0.239/0.220/0.189/0.220/0.238 0.125/0.103/0.096/0.148/0.148/0.122/0.145/0.137/0.148/0.147/0.140/0.126/0.140/0.146 4a 0/0/0/0/0/0/0.003/0/0/0/0/0/0/0 0/0/0/0/0/0/0.003/0/0/0/0/0/0/0 4b 0/0/0/0/0/0/0.090/0/0/0/0/0.001/0.004/0.010 0/0/0/0/0/0/0.045/0/0/0/0/0.005/0.002/0.005 5a 0.022/0.042/0.022/0/0.012/0/0.003/0.003/0/0.001/0/0.003/0/0.004 0.019/0.035/0.019/0/0.011/0/0.003/0.003/0/0.001/0/0.003/0/0.004 5b 0.199/0.235/0.203/0/0.165/0/0.090/0.094/0.010/0.069/0/0.088/0.033/0.103 0.107/0.132/0.100/0/0.087/0/0.045/0.048/0.010/0.035/0/0.045/0.016/0.053 6a 0/0/0/0/0/0/0/0.009/0/0/0.001/0/0/0 0/0/0/0/0/0/0/0.008/0/0/0.001/0/0/0 6b 0/0/0/0/0/0/0.032/0.148/0.010/0/0.054/0.014/0.033/0.020 0/0/0/0/0/0/0.0160/0.078/0.010/0/0.027/0.007/0.016/0.005 15a 0/0.188/0.242/0.248/0.175/0.008/0.182/0.123/0.197/0.212/0.150/0.180/0.188/0.228 0/0.125/0.147/0.142/0.119/0.007/0.115/0.089/0.130/0.136/0.105/0121/0.125/0.143 15b 0/0.188/0.113/0.063/0.199/0.144/0.142/0.237/0.177/0.161/0.220/0.195/0.190/0.238 0/0.125/0.083/0.050/0.131/0.075/0.196/0.054/0.120/0.111/0.140/0.129/0.127/0.098 The Batek subgroup is assumed as donor and father populations for transfusion and gestation, respectively. HPA data for Banjar, Bugis, Champa, Jawa, Kelantan, Malays, Chinese, and Indians were obtained from Wan Syafawati et al.15 and Tan et al.16 HPA = human platelet antigen; B = Batek; W = Che Wong; K = Kensiu; L = Lanoh; S = Semai; O = Orang Kanaq; BA = Banjar; BU = Bugis; C = Champa; J = Jawa; KE = Kelantan; M = Malays; CH = Chinese; I = Indians; > = donor to recipient and father to mother population for random platelet transfusion and gestation, respectively.

Table 8. Hypothetical transfusion and gestation HPA alloimmunization risks between pairs of Che Wong and other Malaysian subpopulations

HPA Transfusion Gestation W>B/W/K/L/S/O/BA/BU/C/J/KE/M/CH/I W>B/W/K/L/S/O/BA/BU/C/J/KE/M/CH/I 1a 0/0/0.001/0/0/0.001/0/0/0/0/0/0/0/0.013 0/0/0.009/0/0.009/0/0/0/0/0/0/0/0/0.012 1b 0/0/0.075/0/0.039/0/0/0/0.038/0/0/0.047/0/0.172 0/0/0.039/0/0.012/0/0/0/0.019/0/0/0.024/0/0.090 2a 0/0/0/0/0/0/0.003/0/0.001/0/0.003/0.001/0.001/0.002 0/0/0/0/0/0/0.003/0/0.971/0/0.003/0.001/0.001/0.002 2b 0/0/0/0/0/0/0.090/0/0.054/0/0.099/0.068/0.061/0.072 0/0/0/0/0/0/0.045/0/0.029/0/0.051/0.034/0.031/0.037 3a 0.188/0.222/0.016/0.113/0.096/0.032/0.125/0.159/0.093/0.119/0.150/0.186/0.149/0.123 0.125/0.141/0.014/0.083/0.072/0.027/0.091/0.110/0.070/0.087/0.105/0.124/0.104/0.089 3b 0.147/0.188/0.179/0.241/0.248/0.221/0.235/0.213/0.248/0.239/0.220/0.189/0.220/0.238 0.125/0.103/0.096/0.148/0.148/0.122/0.145/0.137/0.148/0.147/0.140/0.126/0.140/0.146 4a 0/0/0/0/0/0/0.003/0/0/0/0/0/0/0 0/0/0/0/0/0/0.003/0/0/0/0/0/0/0 4b 0/0/0/0/0/0/0.090/0/0/0/0/0.001/0.004/0.010 0/0/0/0/0/0/0.045/0/0/0/0/0.005/0.002/0.005 5a 0.022/0.042/0.022/0/0.012/0/0.003/0.003/0/0.001/0/0.003/0/0.004 0.019/0.035/0.019/0/0.011/0/0.003/0.003/0/0.001/0/0.003/0/0.004 5b 0.199/0.235/0.203/0/0.165/0/0.090/0.094/0.010/0.069/0/0.088/0.033/0.103 0.107/0.132/0.100/0/0.087/0/0.045/0.048/0.010/0.035/0/0.045/0.016/0.053 6a 0/0/0/0/0/0/0/0.009/0/0/0.001/0/0/0 0/0/0/0/0/0/0/0.008/0/0/0.001/0/0/0 6b 0/0/0/0/0/0/0.032/0.148/0.010/0/0.054/0.014/0.033/0.020 0/0/0/0/0/0/0.032/0.148/0.010/0/0.054/0.014/0.033/0.020 15a 0/0.188/0.242/0.248/0.175/0.008/0.182/0.123/0.197/0.212/0.150/0.180/0.188/0.228 0/0.125/0.147/0.142/0.119/0.007/0.115/0.089/0.130/0.136/0.105/0.121/0.125/0.143 15b 0/0.188/0.113/0.063/0.199/0.144/0.142/0.237/0.177/0.161/0.220/0.195/0.190/0.238 0/0.125/0.083/0.050/0.131/0.075/0.196/0.054/0.120/0.111/0.140/0.129/0.127/0.098 The Che Wong subgroup was assumed as donor and father populations for transfusion and gestation, respectively. HPA data for Banjar, Bugis, Champa, Jawa, Kelantan, Malays, Chinese, and Indians were obtained from Wan Syafawati et al.15 and Tan et al.16 HPA = human platelet antigen; B = Batek; W = Che Wong; K = Kensiu; L = Lanoh; S = Semai; O = Orang Kanaq; BA = Banjar; BU = Bugis; C = Champa; J = Jawa; KE = Kelantan; M = Malays; CH = Chinese; I = Indians; > = donor to recipient and father to mother population for random platelet transfusion and gestation, respectively.

152 IMMUNOHEMATOLOGY, Volume 32, Number 4, 2016 HPA diversity in Peninsular Malaysia

Table 9. Hypothetical transfusion and gestation HPA alloimmunization risks between pairs of Kensiu and other Malaysian subpopulations

HPA Transfusion Gestation K>B/W/K/L/S/O/BA/BU/C/J/KE/M/CH/I K>B/W/K/L/S/O/BA/BU/C/J/KE/M/CH/I 1a 0/0/0.001/0/0.001/0/0/0/0/0/0/0/0/0.013 0/0/0.009/0/0.009/0/0/0/0/0/0/0/0/0.012 1b 0/0/0.075/0/0.039/0/0/0/0.038/0/0/0.047/0/0.172 0/0/0.039/0/0.012/0/0/0/0.019/0/0/0.024/0/0.090 2a 0/0/0/0/0/0/0.003/0/0.001/0/0.003/0.001/0.001/0.002 0/0/0/0/0/0/0.003/0/0.971/0/0.003/0.001/0.001/0.002 2b 0/0/0/0/0/0/0.090/0/0.054/0/0.099/0.068/0.061/0.072 0/0/0/0/0/0/0.045/0/0.029/0/0.051/0.034/0.031/0.037 3a 0.188/0.222/0.016/0.113/0.096/0.032/0.125/0159/0.093/0.119/0.150/0.186/0.149/0.123 0.125/0.141/0.014/0.083/0.072/0.027/0.091/0.110/0.070/0.087/ 0.105/0.124/0.104/0.089 3b 0.188/0.147/0.179/0.241/0.248/0.221/0.235/0.213/0.248/0.239/0.220/0.189/0.220/0.238 0.125/0.103/0.096/0.148/0.148/0.122/0.145/0.137/0.148/0.147/ 0.140/0.126/0.140/0.146 4a 0/0/0/0/0/0/0.003/0/0/0/0/0/0/0 0/0/0/0/0/0/0.003/0/0/0/0/0/0/0 4b 0/0/0/0/0/0/0.090/0/0/0/0/0.001/0.004/0.010 0/0/0/0/0/0/0.045/0/0/0/0/0.005/0.002/0.005 5a 0.022/0.042/0.022/0/0.012/0/0.003/0.003/0/0.001/0/0.003/0/0.004 0.019/0.035/0.019/0/0.011/0/.003/0.003/0/0.001/0/0.003/0/0.004 5b 0.199/0.235/0.203/0/0.165/0/0.090/0.094/0.010/0.069/0/0.088/0.033/0.103 0.107/0.132/0.100/0/0.087/0/0.045/0.048/0.010/0.035/0/0.045/0.016/0.053 6a 0/0/0/0/0/0/0/0.009/0/0/0.001/0/0/0 0/0/0/0/0/0/0/0.008/0/0/0.001/0/0/0 6b 0/0/0/0/0/0/0.032/0.148/0.010/0/0.054/0.014/0.033/0.020 0/0/0/0/0/0/0.032/0.148/0.010/0/0.054/0.014/0.033/0.020 15a 0/0.188/0.242/0.248/0.175/0.008/0.182/0.123/0.197/0.212/0.150/0.180/0.188/0.228 0/0.125/0.147/0.142/0.119/0.007/0.115/0.089/0.130/0.136/0.105/0121/0.125/0.143 15b 0/0.188/0.113/0.199/0.144/0.063/0.142/0.237/0.177/0.161/0.220/0.195/0.190/0.238 0/0.125/0.083/0.050/0.131/0.075/0.196/0.054/0.120/0.111/0.140/0.129/0.127/0.098 The Kensiu subgroup is assumed as donor and father populations for transfusion and gestation, respectively. HPA data for Banjar, Bugis, Champa, Jawa, Kelantan, Malays, Chinese, and Indians were obtained from Wan Syafawati et al.15 and Tan et al.16 HPA = human platelet antigen; B = Batek; W = Che Wong; K = Kensiu; L = Lanoh; S = Semai; O = Orang Kanaq; BA = Banjar; BU = Bugis; C = Champa; J = Jawa; KE = Kelantan; M = Malays; CH = Chinese; I = Indians; > = donor to recipient and father to mother population for random platelet transfusion and gestation, respectively.

Table 10. Hypothetical transfusion and gestation HPA alloimmunization risks between pairs of Lanoh and other Malaysian subpopulations

HPA Transfusion Gestation L>B/W/K/L/S/O/BA/BU/C/J/KE/M/CH/I L>B/W/K/L/S/O/BA/BU/C/J/KE/M/CH/I 1a 0/0/0.001/0/0.001/0/0/0/0/0/0/0/0/0.013 0/0/0.009/0/0.009/0/0/0/0/0/0/0/0/0.012 1b 0/0/0.075/0/0.039/0/0/0/0.038/0/0/0.047/0/0.172 0/0/0.039/0/0.012/0/0/0/0.019/0/0/0.024/0/0.090 2a 0/0/0/0/0/0/0.003/0/0.001/0/0.003/0.001/0.001/0.002 0/0/0/0/0/0/0.003/0/0.971/0/0.003/0.001/0.001/0.002 2b 0/0/0/0/0/0/0.090/0/0.054/0/0.099/0.068/0.061/0.072 0/0/0/0/0/0/0.045/0/0.029/0/0.051/0.034/0.031/0.037 3a 0.188/0.222/0.016/0.113/0.096/0.032/0.125/0.159/0.093/0.119/0.150/0.186/0.149/0.123 0.125/0.141/0.014/0.083/0.072/0.027/0.091/0.110/0.070/0.087/0.105/0.124/0.104/0.089 3b 0.188/0.222/0.016/0.241/0.248/0.032/0.235/0.213/0.248/0.239/0.220/0.189/0.220/0.238 0.125/0.103/0.096/0.148/0.148/0.122/0.145/0.137/0.148/0.147/0.140/0.126/0.140/0.146 4a 0/0/0/0/0/0/0.003/0/0/0/0/0/0/0 0/0/0/0/0/0/0.003/0/0/0/0/0/0/0 4b 0/0/0/0/0/0/0.090/0/0/0/0/0.001/0.004/0.010 0/0/0/0/0/0/0.045/0/0/0/0/0.005/0.002/0.005 5a 0.022/0.042/0.022/0/0.012/0/0.003/0.003/0/0.001/0/0.003/0/0.004 0.019/0.035/0.019/0/0.011/0/0.003/0.003/0/0.001/0/0.003/0/0.004 5b 0.199/0.235/0.203/0/0.165/0/0.090/0.094/0.010/0.069/0/0.088/0.033/0.103 0.107/0.132/0.100/0/0.087/0/0.045/0.048/0.010/0.035/0/0.045/0.016/0.053 6a 0/0/0/0/0/0/0/0.009/0/0/0.001/0/0/0 0/0/0/0/0/0/0/0.008/0/0/0.001/0/0/0 6b 0/0/0/0/0/0/0.032/0.148/0.010/0/0.054/0.014/0.033/0.020 0/0/0/0/0/0/0.032/0.148/0.010/0/0.054/0.014/0.033/0.020 15a 0/0.188/0.242/0.248/0.175/0.008/0.182/0.123/0.197/0.212/0.150/0.180/0.188/0.228 0/0.125/0.147/0.050/0.119/0.007/0.115/0.089/0.130/0.136/0.105/0.121/0.125/0.143 15b 0/0.188/0.113/0.063/0.199/0.144/0.142/0.237/0.177/0.161/0.220/0.195/0.190/0.238 0/0.125/0.083/0.050/0.131/0.075/0.196/0.054/0.120/0.111/0.140/0.129/0.127/0.098 The Lanoh subgroup is assumed as donor and father populations for transfusion and gestation, respectively. HPA data for Banjar, Bugis, Champa, Jawa, Kelantan, Malays, Chinese, and Indians were obtained from Wan Syafawati et al.15 and Tan et al.16 HPA = human platelet antigen; B = Batek; W = Che Wong; K = Kensiu; L = Lanoh; S = Semai; O = Orang Kanaq; BA = Banjar; BU = Bugis; C = Champa; J = Jawa; KE = Kelantan; M = Malays; CH = Chinese; I = Indians; > = donor to recipient and father to mother population for random platelet transfusion and gestation, respectively.

IMMUNOHEMATOLOGY, Volume 32, Number 4, 2016 153 W.U.W. Syafawati et al.

Table 11. Hypothetical transfusion and gestation HPA alloimmunization risks between pairs of Semai and other Malaysian subpopulations

HPA Transfusion Gestation S>B/W/K/L/S/O/BA/BU/C/J/KE/M/CH/I S>B/W/K/L/S/O/BA/BU/C/J/KE/M/CH/I 1a 0/0/0.001/0/0.001/0/0/0/0/0/0/0/0/0.013 0/0/0.009/0/0.009/0/0/0/0/0/0/0/0/0.012 1b 0/0/0.075/0/0.039/0/0/0/0.038/0/0/0.047/0/0.172 0/0/0.039/0/0.012/0/0/0/0.019/0/0/0.024/0/0.09 2a 0/0/0/0/0/0/0.003/0/0.001/0/0.003/0.001/0.001/0.002 0/0/0/0/0/0/0.003/0/0.971/0/0.003/0.001/0.001/0.002 2b 0/0/0/0/0/0/0.090/0/0.054/0/0.099/0.068/0.061/0.072 0/0/0/0/0/0/0.045/0/0.029/0/0.051/0.034/0.031/0.037 3a 0.188/0.222/0.016/0.113/0.096/0.032/0.125/0.159/0.093/0.119/0.150/0.186/0.149/0.123 0.125/0.141/0.014/0.083/0.072/0.027/0.091/0.110/0.070/0.087/0.105/0.124/0.104/0.089 3b 0.188/0.147/0.179/0.241/0.248/0.221/0.235/0.213/0.248/0.239/0.220/0.189/0.220/0.238 0.125/0.103/0.148/0.122/0.148/0.096/0.145/0.137/0.148/0.147/0.140/0.126/0.140/0.146 4a 0/0/0/0/0/0/0.003/0/0/0/0/0/0/0 0/0/0/0/0/0/0.003/0/0/0/0/0/0/0 4b 0/0/0/0/0/0/0.090/0/0/0/0/0.001/0.004/0.010 0/0/0/0/0/0/0.045/0/0/0/0/0.005/0.002/0.005 5a 0.022/0.042/0.022/0/0.012/0/0.003/0.003/0/0.001/0/0.003/0/0.004 0.019/0.035/0.019/0/0.011/0/0.003/0/0.001/0/0.003/0/0.004 5b 0.199/0.235/0.203/0/0.165/0/0.090/0.094/0.010/0.069/0/0.088/0.033/0.103 0.107/0.132/0.100/0/0.087/0/0.045/0.048/0.010/0.035/0/0.045/0.016/0.053 6a 0/0/0/0/0/0/0/0.009/0/0/0.001/0/0/0 0/0/0/0/0/0/0/0.008/0/0/0.001/0/0/0 6b 0/0/0/0/0/0/0.032/0.148/0.010/0/0.054/0.014/0.033/0.020 0/0/0/0/0/0/0.032/0.148/0.010/0/0.054/0.014/0.033/0.020 15a 0/0.188/0.242/0.248/0.175/0.008/0.182/0.123/0.197/0.212/0.150/0.180/0.188/0.228 0/0.125/0.147/0.142/0.119/0.007/0.115/0.089/0.130/0.136/0.105/0.121/0.125/0.143 15b 0/0.188/0.113/0.063/0.199/0.144/0.142/0.237/0.177/0.161/0.220/0.195/0.190/0.238 0/0.125/0.083/0.050/0.131/0.075/0.196/0.054/0.120/0.111/0.140/0.129/0.127/0.098 The Semai subgroup is assumed as donor and father populations for transfusion and gestation, respectively. HPA data for Banjar, Bugis, Champa, Jawa, Kelantan, Malays, Chinese, and Indians were obtained from Wan Syafawati et al.15 and Tan et al.16 HPA = human platelet antigen; B = Batek; W = Che Wong; K = Kensiu; L = Lanoh; S = Semai; O = Orang Kanaq; BA = Banjar; BU = Bugis; C = Champa; J = Jawa; KE = Kelantan; M = Malays; CH = Chinese; I = Indians; > = donor to recipient and father to mother population for random platelet transfusion and gestation, respectively.

Table 12. Hypothetical transfusion and gestation HPA alloimmunization risks between pairs of Orang Kanaq and other Malaysian subpopulations

HPA Transfusion Gestation O>B/W/K/L/S/O/BA/BU/C/J/KE/M/CH/I O>B/W/K/L/S/O/BA/BU/C/J/KE/M/CH/I 1a 0/0/0.001/0/0.001/0/0/0/0/0/0/0/0/0.013 0/0/0.009/0/0.009/0/0/0/0/0/0/0/0/0.012 1b 0/0/0.075/0/0.039/0/0/0/0.038/0/0/0.047/0/0.172 0/0/0.390/0/0.012/0/0/0/0.019/0/0/0.024/0/0.090 2a 0/0/0/0/0/0/0.003/0/0.001/0/0.003/0.001/0.001/0.002 0/0/0/0/0/0/0.003/0/0.971/0/0.003/0.001/0.001/0.002 2b 0/0/0/0/0/0/0.090/0/0.054/0/0.099/0.068/0.061/0.072 0/0/0/0/0/0/0.045/0/0.029/0/0.051/0.034/0.031/0.037 3a 0.188/0.222/0.016/0.113/0.096/0.032/0.125/0.159/0.093/0.119/0.150/0.186/0.149/0.123 0.125/0.141/0.014/0.083/0.072/0.027/0.091/0.110/0.070/0.087/0.105/0.124/0.104/0.089 3b 0.188/0.147/0.179/0.241/0.248/0.221/0.235/0.213/0.248/0.239/0.220/0.189/0.220/0.238 0.125/0.103/0.096/0.148/0.148/0.122/0.145/0.137/0.148/0.147/0.140/0.126/0.140/0.146 4a 0/0/0/0/0/0/0.003/0/0/0/0/0/0/0 0/0/0/0/0/0/0.003/0/0/0/0/0/0/0 4b 0/0/0/0/0/0/0.090/0/0/0/0/0.001/0.004/0.010 0/0/0/0/0/0/0.045/0/0/0/0/0.005/0.002/0.005 5a 0.022/0.042/0.022/0/0.012/0/0.003/0.003/0/0.001/0/0.003/0/0.004 0.019/0.035/0.019/0/0.011/0/0.003/0.003/0/0.001/0/0.003/0/0.004 5b 0.199/0.235/0.203/0/0.165/0/0.090/0.094/0.010/0.069/0/0.088/0.033/0.103 0.107/0.132/0.100/0/0.087/0/0.045/0.048/0.010/0.035/0/0.045/0.016/0.053 6a 0/0/0/0/0/0/0/0.009/0/0/0.001/0/0/0 0/0/0/0/0/0/0/0.008/0/0/0.001/0/0/0 6b 0/0/0/0/0/0/0.032/0.148/0.010/0/0.054/0.014/0.033/0.020 0/0/0/0/0/0/0.032/0.148/0.010/0/0.054/0.014/0.033/0.020 15a 0/0.188/0.242/0.248/0.175/0.008/0.182/0.123/0.197/0.212/0.150/0.180/0.188/0.228 0/0.125/0.083/0.050/0.131/0.115/0.075/0.089/0.130/0.136/0.105/0.121/0.125/0.143 15b 0/0.188/0.113/0.063/0.199/0.144/0.142/0.237/0.177/0.161/0.220/0.195/0.190/0.238 0/0.125/0.083/0.050/0.131/0.075/0.196/0.054/0.120/0.111/0.140/0.129/0.127/0.098 The Orang Kanaq subgroup is assumed as donor and father populations for transfusion and gestation, respectively. HPA data for Banjar, Bugis, Champa, Jawa, Kelantan, Malays, Chinese, and Indians were obtained from Wan Syafawati et al.15 and Tan et al.16 HPA = human platelet antigen; B = Batek; W = Che Wong; K = Kensiu; L = Lanoh; S = Semai; O = Orang Kanaq; BA = Banjar; BU = Bugis; C = Champa; J = Jawa; KE = Kelantan; M = Malays; CH = Chinese; I = Indians; > = donor to recipient and father to mother population for random platelet transfusion and gestation, respectively.

154 IMMUNOHEMATOLOGY, Volume 32, Number 4, 2016 HPA diversity in Peninsular Malaysia

Table 13. Hypothetical transfusion and gestation HPA alloimmunization risks between pairs of Banjar and other Malaysian subpopulations

HPA Transfusion Gestation BA>B/W/K/L/S/O/BA/BU/C/J/KE/M/CH/I BA>B/W/K/L/S/O/BA/BU/C/J/KE/M/CH/I 1a 0/0/0.009/0/0.009/0/0/0/0/0/0/0/0/0.013 0/0/0.001/0/0.001/0/0/0/0/0/0/0/0/0.012 1b 0/0/0.075/0/0.039/0/0/0/0.038/0/0/0.047/0/0.172 0/0/0.039/0/0.012/0/0/0/0.019/0/0/0.024/0/0.090 2a 0.002/0/0/0/0/0/0.003/0/0.001/0/0/0.003/0.001/0.001 0/0/0/0/0/0/0.003/0/0.001/0/0.003/0.001/0.001/0.002 2b 0/0/0/0/0/0/0.090/0/0.054/0/0.099/0.068/0.061/0.072 0/0/0/0/0/0/0.045/0/0.027/0/0.051/0.034/0.031/0.037 3a 0.188/0.222/0.016/0.241/0.096/0.032/0.125/0.159/0.093/0.119/0.150/0.186/0.149/0.123 0.125/0.141/0.014/0.083/0.072/0.027/0.091/0.110/0.070/0.087/0.105/0.124/0.104/0.089 3b 0.188/0.147/0.179/0.241/0.248/0.221/0.235/0.213/0.248/0.239/0.220/0.189/0.220/0.238 0.125/0.103/0.096/0.148/0.148/0.122/0.145/0.137/0.148/0.147/0.140/0.126/0.140/0.146 4a 0/0/0/0/0/0/0.003/0/0/0/0/0/0/0 0/0/0/0/0/0/0.003/0/0/0/0/0/0/0 4b 0/0/0/0/0/0/0.090/0/0/0/0/0.001/0.004/0.010 0/0/0/0/0/0/0.045/0/0/0/0/0.005/0.002/0.005 5a 0.022/0.042/0.022/0/0.012/0/0.003/0.003/0/0.001/0/0.003/0/0.004 0.019/0.035/0.019/0/0.011/0/0.003/0.003/0/0.001/0/0.003/0/0.004 5b 0.199/0.235/0.203/0/0.165/0/0.090/0.094/0.010/0.069/0/0.088/0.033/0.103 0.107/0.132/0.100/0/0.087/0/0.045/0.048/0.010/0.035/0/0.045/0.016/0.053 6a 0/0/0/0/0/0/0/0.009/0/0/0.001/0/0/0 0/0/0/0/0/0/0/0.008/0/0/0.001/0/0/0 6b 0/0/0/0/0/0/0.032/0.148/0.010/0/0.054/0.014/0.033/0.020 0/0/0/0/0/0/0.016/0.078/0.010/0/0.027/0.007/0.016/0.005 15a 0/0.188/0.242/0.248/0.175/0.008/0.182/0.123/0.197/0.212/0.150/0.180/0.188/0.288 0/0.125/0.147/0.142/0.119/0.007/0.115/0.089/0.130/0.136/0.105/0.121/0.125/0.143 15b 0/0.188/0.113/0.063/0.199/0.144/0.142/0.237/0.177/0.161/0.220/0.195/0.190/0.138 0/0.125/0.083/0.050/0.131/0.075/0.096/0.054/0.120/0.111/0.140/0.129/0.127/0.098 The Banjar subgroup is assumed as donor and father populations for transfusion and gestation, respectively. HPA data for Banjar, Bugis, Champa, Jawa, Kelantan, Malays, Chinese, and Indians were obtained from Wan Syafawati et al.15 and Tan et al.16 HPA = human platelet antigen; B = Batek; W = Che Wong; K = Kensiu; L = Lanoh; S = Semai; O = Orang Kanaq; BA = Banjar; BU = Bugis; C = Champa; J = Jawa; KE = Kelantan; M = Malays; CH = Chinese; I = Indians; > = donor to recipient and father to mother population for random platelet transfusion and gestation, respectively.

Table 14. Hypothetical transfusion and gestation HPA alloimmunization risks between pairs of Bugis and other Malaysian subpopulations

HPA Transfusion Gestation BU>B/W/K/L/S/O/BA/BU/C/J/KE/M/CH/I BU>B/W/K/L/S/O/BA/BU/C/J/KE/M/CH/I 1a 0/0/0.009/0/0.009/0/0/0/0/0/0/0/0/0.013 0/0/0.001/0/0.001/0/0/0/0/0/0/0/0/0.012 1b 0/0/0.075/0/0.039/0/0/0/0.038/0/0/0.047/0/0.172 0/0/0.039/0/0.012/0/0/0/0.019/0/0/0.024/0/0.090 2a 0/0/0/0/0/0/0.003/0/0.001/0/0.003/0.001/0.001/0.002 0/0/0/0/0/0/0.003/0/0.001/0/0.003/0.001/0.001/0.002 2b 0/0/0/0/0/0/0.090/0/0.054/0/0.099/0.068/0.061/0.072 0/0/0/0/0/0/0/0.045/0.027/0/0.051/0.034/0.031/0.037 3a 0.188/0.222/0.016/0.241/0.096/0.032/0.125/0.159/0.093/0.119/0.150/0.186/0.149/0.123 0.125/0.141/0.014/0.083/0.072/0.027/0.091/0.110/0.070/0.087/0.105/0.124/0.104/0.089 3b 0.188/0.147/0.179/0.241/0.248/0.221/0.235/0.213/0.248/0.239/0.220/0.189/0.220/0.238 0.125/0.103/0.096/0.148/0.148/0.122/0.145/0.137/0.148/0.147/0.140/0.126/0.140/0.146 4a 0/0/0/0/0/0/0.003/0/0/0/0/0/0/0 0/0/0/0/0/0/0.003/0/0/0/0/0/0/0 4b 0/0/0/0/0/0/0.090/0/0/0/0/0.001/0.004/0.010 0/0/0/0/0/0/0.045/0/0/0/0/0.005/0.002/0.005 5a 0.004/0.022/0.042/0.022/0/0.012/0/0.003/0.003/0/0.001/0/0.003/0 0.019/0.035/0.019/0/0.011/0/0.003/0.003/0/0.001/0/0.003/0/0.004 5b 0.199/0.235/0.203/0/0.165/0/0.090/0.094/0.010/0.069/0/0.088/0.033/0.103 0.107/0.132/0.100/0/0.087/0/0.045/0.048/0/0.035/0/0.045/0.016/0.053 6a 0/0/0/0/0/0/0/0.009/0/0/0.001/0/0/0 0/0/0/0/0/0/0/0.008/0/0/0.001/0/0/0 6b 0/0/0/0/0/0/0.032/0.148/0.010/0/0.054/0.014/0.033/0.020 0/0/0/0/0/0/0.016/0.078/0.010/0/0.027/0.007/0.016/0.005 15a 0/0.188/0.242/0.248/0.175/0.008/0.182/0.123/0.197/0.212/0.150/0.180/0.188/0.228 0/0.125/0.147/0.142/0.119/0.007/0.115/0.089/0.130/0.136/0.105/0.121/0.125/0.143 15b 0/0.188/0.113/0.063/0.199/0.144/0.142/0.237/0.177/0.161/0.220/0.195/0.190/0.138 0/0.125/0.083/0.050/0.131/0.075/0.096/0.054/0.120/0.111/0.140/0.129/0.127/0.098 The Bugis subgroup is assumed as donor and father populations for transfusion and gestation, respectively. HPA data for Banjar, Bugis, Champa, Jawa, Kelantan, Malays, Chinese, and Indians were obtained from Wan Syafawati et al.15 and Tan et al.16 HPA = human platelet antigen; B = Batek; W = Che Wong; K = Kensiu; L = Lanoh; S = Semai; O = Orang Kanaq; BA = Banjar; BU = Bugis; C = Champa; J = Jawa; KE = Kelantan; M = Malays; CH = Chinese; I = Indians; > = donor to recipient and father to mother population for random platelet transfusion and gestation, respectively.

IMMUNOHEMATOLOGY, Volume 32, Number 4, 2016 155 W.U.W. Syafawati et al.

Table 15. Hypothetical transfusion and gestation HPA alloimmunization risks between pairs of Champa and other Malaysian subpopulations

HPA Transfusion Gestation C>B/W/K/L/S/O/BA/BU/C/J/KE/M/CH/I C>B/W/K/L/S/O/BA/BU/C/J/KE/M/CH/I 1a 0/0/0.009/0/0.009/0/0/0/0/0/0/0/0/0.013 0/0/0.001/0/0.001/0/0/0/0/0/0/0/0/0.012 1b 0/0/0.075/0/0.039/0/0/0/0.038/0/0/0.047/0/0.172 0/0/0.039/0/0.012/0/0/0/0.019/0/0/0.024/0/0.090 2a 0/0/0/0/0/0/0.003/0/0.001/0/0.003/0.001/0.001/0.002 0/0/0/0/0/0/0.003/0/0.001/0/0.003/0.001/0.001/0.002 2b 0/0/0/0/0/0/0.090/0/0.054/0/0.099/0.068/0.061/0.072 0/0/0/0/0/0/0.045/0/0.027/0/0.051/0.034/0.031/0.037 3a 0.188/0.222/0.016/0.241/0.096/0.032/0.125/0.159/0.093/0.119/0.150/0.186/0.149/0.123 0.125/0.141/0.014/0.083/0.072/0.027/0.091/0.110/0.070/0.087/0.105/0.124/0.104/0.089 3b 0.188/0.147/0.179/0.241/0.248/0.221/0.235/0.213/0.248/0.239/0.220/0.189/0.220/0.238 0.125/0.103/0.096/0.148/0.148/0.122/0.145/0.137/0.148/0.147/0.140/0.126/0.140/0.146 4a 0/0/0/0/0/0/0.003/0/0/0/0/0/0/0 0/0/0/0/0/0/0/0.003/0/0/0/0/0/0 4b 0/0/0/0/0/0/0.090/0/0/0/0/0.001/0.004/0.010 0/0/0/0/0/0/0/0.045/0/0/0/0.005/0.002/0.005 5a 0.022/0.042/0.022/0/0.012/0/0.003/0.003/0/0.001/0/0.003/0/0.004 0.019/0.035/0.019/0/0.011/0/0.003/0.003/0/0.001/0/0.003/0/0.004 5b 0.199/0.235/0.203/0/0.165/0/0.090/0.094/0.010/0.069/0/0.088/0.033/0.103 0.107/0.132/0.100/0/0.087/0/0.045/0.048/0.010/0.035/0/0.045/0.016/0.053 6a 0/0/0/0/0/0/0/0.009/0/0/0.001/0/0/0 0/0/0/0/0/0/0/0.008/0/0/0.001/0/0/0 6b 0/0/0/0/0/0/0.032/0.148/0.010/0/0.054/0.014/0.033/0.020 0/0/0/0/0/0/0.016/0.078/0.010/0/0.027/0.007/0.016/0.005 15a 0/0.188/0.242/0.248/0.175/0.008/0.182/0.123/0.197/0.212/0.150/0.180/0.188/0.228 0/0.125/0.147/0.142/0.119/0.007/0.115/0.089/0.130/0.136/0.105/0.121/0.125/0.143 15b 0/0.188/0.113/0.063/0.199/0.144/0.142/0.237/0.177/0.161/0.220/0.195/0.190/0.138 0/0.125/0.083/0.050/0.131/0.075/0.096/0.054/0.120/0.111/0.140/0.129/0.127/0.098 The Champa subgroup is assumed as donor and father populations for transfusion and gestation, respectively. HPA data for Banjar, Bugis, Champa, Jawa, Kelantan, Malays, Chinese, and Indians were obtained from Wan Syafawati et al.15 and Tan et al.16 HPA = human platelet antigen; B = Batek; W = Che Wong; K = Kensiu; L = Lanoh; S = Semai; O = Orang Kanaq; BA = Banjar; BU = Bugis; C = Champa; J = Jawa; KE = Kelantan; M = Malays; CH = Chinese; I = Indians; > = donor to recipient and father to mother population for random platelet transfusion and gestation, respectively.

Table 16. Hypothetical transfusion and gestation HPA alloimmunization risks between pairs of Jawa and other Malaysian subpopulations

HPA Transfusion Gestation J>B/W/K/L/S/O/BA/BU/C/J/KE/M/CH/I J>B/W/K/L/S/O/BA/BU/C/J/KE/M/CH/I 1a 0/0/0.009/0/0.009/0/0/0/0/0/0/0/0/0.013 0/0/0.001/0/0.001/0/0/0/0/0/0/0/0/0.012 1b 0/0/0.075/0/0.039/0/0/0/0.038/0/0/0.047/0/0.172 0/0/0.039/0/0.012/0/0/0/0.019/0/0/0.024/0/0.090 2a 0/0/0/0/0/0/0.003/0/0.001/0/0.003/0.001/0.001/0.002 0/0/0/0/0/0/0.003/0/0.001/0/0.003/0.001/0.001/0.002 2b 0/0/0/0/0/0/0.090/0/0.054/0/0.099/0.068/0.061/0.072 0/0/0/0/0/0/0.045/0/0.027/0/0.051/0.034/0.031/0.037 3a 0.188/0.222/0.016/0.241/0.096/0.032/0.125/0.159/0.093/0.009/0.150/0.186/0.149/0.123 0.125/0.141/0.014/0.083/0.072/0.027/0.091/0.110/0.070/0.087/0.105/0.124/0.104/0.089 3b 0.188/0.147/0.179/0.241/0.248/0.221/0.235/0.213/0.248/0.239/0.220/0.189/0.220/0.238 0.125/0.103/0.096/0.148/0.148/0.122/0.145/0.137/0.148/0.147/0.140/0.126/0.140/0.146 4a 0/0/0/0/0/0/0/0.003/0/0/0/0/0/0 0/0/0/0/0/0/0.003/0/0/0/0/0/0/0 4b 0/0/0/0/0/0/0/0.090/0/0/0/0.001/0.004/0.010 0/0/0/0/0/0/0.045/0/0/0/0/0.005/0.002/0.005 5a 0.022/0.042/0.022/0/0.012/0/0.003/0.003/0/0.001/0/0.003/0/0.004 0.019/0.035/0.019/0/0.011/0/0.003/0.003/0/0.001/0/0.003/0/0.004 5b 0.199/0.235/0.203/0/0.165/0/0.090/0.094/0.010/0.069/0/0.088/0.033/0.103 0.107/0.132/0.100/0/0.087/0/0.045/0.048/0.010/0.035/0/0.045/0.016/0.053 6a 0/0/0.009/0/0.001/0/0/0/0/0/0/0/0/0 0/0/0/0/0/0/0/0/0.008/0/0.001/0/0/0 6b 0.032/0.148/0.010/0/0.054/0.014/0.033/0.020/0/0/0/0/0/0 0/0/0/0/0/0/0.016/0.078/0.010/0/0.027/0.007/0.016/0.005 15a 0/0.188/0.242/0.248/0.175/0.008/0.182/0.123/0.197/0.212/0.150/0.180/0.188/0.228 0/0.125/0.147/0.142/0.119/0.007/0.115/0.089/0.130/0.136/0.105/0.121/0.125/0.143 15b 0/0.188/0.113/0.063/0.199/0.144/0.142/0.237/0.177/0.161/0.220/0.195/0.190/0.138 0/0.125/0.083/0.050/0.131/0.075/0.096/0.054/0.120/0.111/0.140/0.129/0.127/0.098 The Jawa subgroup is assumed as donor and father populations for transfusion and gestation, respectively. HPA data for Banjar, Bugis, Champa, Jawa, Kelantan, Malays, Chinese, and Indians were obtained from Wan Syafawati et al.15 and Tan et al.16 HPA = human platelet antigen; B = Batek; W = Che Wong; K = Kensiu; L = Lanoh; S = Semai; O = Orang Kanaq; BA = Banjar; BU = Bugis; C = Champa; J = Jawa; KE = Kelantan; M = Malays; CH = Chinese; I = Indians; > = donor to recipient and father to mother population for random platelet transfusion and gestation, respectively.

156 IMMUNOHEMATOLOGY, Volume 32, Number 4, 2016 HPA diversity in Peninsular Malaysia

Table 17. Hypothetical transfusion and gestation HPA alloimmunization risks between pairs of Kelantan and other Malaysian subpopulations

HPA Transfusion Gestation KE>B/W/K/L/S/O/BA/BU/C/J/KE/M/CH/I KE>B/W/K/L/S/O/BA/BU/C/J/KE/M/CH/I 1a 0/0/0.009/0/0.009/0/0/0/0/0/0/0/0/0.013 0/0/0.001/0/0.001/0/0/0/0/0/0/0/0/0.012 1b 0/0/0.075/0/0.039/0/0/0/0.038/0/0.047/0/0/0.172 0/0/0.039/0/0.012/0/0/0/0/0.019/0/0.024/0/0.09 2a 0/0/0/0/0/0/0/0.001/0/0.003/0.003/0.001/0.001/0.002 0/0/0/0/0/0/0.003/0/0.001/0/0.003/0.001/0.001/0.002 2b 0/0/0/0/0/0/0.090/0/0.054/0/0.099/0.068/0.061/0.072 0/0/0/0/0/0/0.045/0/0.027/0/0.051/0.034/0.031/0.037 3a 0.188/0.222/0.016/0.241/0.096/0.032/0.125/0.159/0.093/0.119/0.150/0.186/0.149/0.123 0.125/0.141/0.014/0.083/0.072/0.027/0.091/0.110/0.070/0.087/0.105/0.124/0.104/0.089 3b 0.188/0.147/0.179/0.241/0.248/0.221/0.235/0.213/0.248/0.239/0.220/0.189/0.220/0.238 0.125/0.103/0.096/0.148/0.148/0.122/0.145/0.137/0.148/0.147/0.140/0.126/0.140/0.146 4a 0/0/0/0/0/0/0/0.003/0/0/0/0/0/0 0/0/0/0/0/0/0/0.003/0/0/0/0/0/0 4b 0/0/0/0/0/0/0/0.090/0/0/0/0.001/0.004/0.010 0/0/0/0/0/0/0/0.045/0/0/0/0.005/0.002/0.005 5a 0.022/0.042/0.022/0/0.012/0/0.003/0.003/0/0.001/0/0.003/0/0.004 0.019/0.035/0.019/0/0.011/0/0.003/0.003/0/0.001/0/0.003/0/0.004 5b 0.199/0.235/0.203/0/0.165/0/0.090/0.094/0.010/0.069/0/0.088/0.033/0.103 0.107/0.132/0.100/0/0.087/0/0.045/0.048/0.010/0.035/0/0.045/0.016/0.053 6a 0/0/0/0/0/0/0/0.009/0/0/0.001/0/0/0 0/0/0/0/0/0/0/0.008/0/0/0.001/0/0/0 6b 0/0/0/0/0/0/0.032/0.148/0.010/0/0.054/0.014/0.033/0.020 0/0/0/0/0/0/0.016/0.078/0.010/0/0.027/0.007/0.016/0.005 15a 0/0.188/0.242/0.248/0.175/0.008/0.182/0.123/0.197/0.212/0.150/0.180/0.188/0.288 0/0.125/0.147/0.142/0.119/0.007/0.115/0.089/0.130/0.136/0.105/0.121/0.125/0.143 15b 0/0.188/0.113/0.063/0.199/0.144/0.142/0.237/0.177/0.161/0.220/0.195/0.190/0.138 0/0.125/0.083/0.050/0.131/0.075/0.096/0.054/0.120/0.111/0.140/0.129/0.127/0.098 The Kelantan subgroup is assumed as donor and father populations for transfusion and gestation, respectively. HPA data for Banjar, Bugis, Champa, Jawa, Kelantan, Malays, Chinese, and Indians were obtained from Wan Syafawati et al.15 and Tan et al.16 HPA = human platelet antigen; B = Batek; W = Che Wong; K = Kensiu; L = Lanoh; S = Semai; O = Orang Kanaq; BA = Banjar; BU = Bugis; C = Champa; J = Jawa; KE = Kelantan; M = Malays; CH = Chinese; I = Indians; > = donor to recipient and father to mother population for random platelet transfusion and gestation, respectively.

Table 18. Hypothetical transfusion and gestation HPA alloimmunization risks between pairs of Malays and other Malaysian subpopulations

HPA Transfusion Gestation M>B/W/K/L/S/O/BA/BU/C/J/KE/M/CH/I M>B/W/K/L/S/O/BA/BU/C/J/KE/M/CH/I 1a 0/0/0.009/0/0.009/0/0/0/0/0/0/0/0/0.013 0/0/0.001/0/0.001/0/0/0/0/0/0/0/0/0.012 1b 0/0/0.075/0/0.039/0/0/0/0.038/0/0/0.047/0/0.172 0/0/0.039/0/0.012/0/0/0/0.019/0/0/0.024/0/0.09 2a 0/0/0/0/0/0/0.003/0/0.001/0/0.003/0.001/0.001/0.002 0/0/0/0/0/0/0.003/0/0.001/0/0.003/0.001/0.001/0.002 2b 0/0/0/0/0/0/0.090/0/0.054/0/0.099/0.068/0.061/0.072 0/0/0/0/0/0/0.045/0/0.027/0/0.051/0.034/0.031/0.037 3a 0.188/0.222/0.016/0.241/0.096/0.032/0.125/0.159/0.093/0.119/0.150/0.186/0.149/0.123 0.125/0.141/0.014/0.083/0.072/0.027/0.091/0.110/0.070/0.087/0.105/0.124/0.104/0.089 3b 0.188/0.147/0.179/0.241/0.248/0.221/0.235/0.213/0.248/0.239/0.220/0.189/0.220/0.238 0.125/0.103/0.096/0.148/0.148/0.122/0.145/0.137/0.148/0.147/0.140/0.126/0.140/0.146 4a 0/0/0/0/0/0/0/0/0/0.003/0/0/0/0 0/0/0/0/0/0/0.003/0/0/0/0/0/0/0 4b 0.001/0.004/0.010/0.090/0/0/0/0/0/0/0/0/0/0 0/0/0/0/0/0/0.045/0/0/0/0/0.005/0.002/0.005 5a 0.022/0.042/0.022/0/0.012/0/0.003/0.003/0/0.001/0/0.003/0/0.004 0.019/0.035/0.019/0/0.011/0/0.003/0.003/0/0.001/0/0.003/0/0.004 5b 0.199/0.235/0.203/0/0.165/0/0.090/0.094/0.010/0.069/0/0.088/0.033/0.103 0.107/0.132/0.100/0/0.087/0/0.045/0.048/0.010/0.035/0/0.045/0.016/0.053 6a 0/0/0/0/0/0/0/0.009/0/0/0.001/0/0/0 0/0/0/0/0/0/0/0.008/0/0/0.001/0/0/0 6b 0/0/0/0/0/0/0.032/0.148/0.010/0/0.054/0.014/0.033/0.020 0/0/0/0/0/0/0.016/0.078/0.010/0/0.027/0.007/0.016/0.005 15a 0/0.188/0.242/0.248/0.175/0.008/0.182/0.123/0.197/0.212/0.150/0.180/0.188/0.288 0/0.125/0.147/0.142/0.119/0.007/0.115/0.089/0.130/0.136/0.105/0.121/0.125/0.143 15b 0/0.188/0.113/0.063/0.199/0.144/0.142/0.237/0.177/0.161/0.220/0.195/0.190/0.138 0/0.125/0.083/0.050/0.131/0.075/0.096/0.054/0.120/0.111/0.140/0.129/0.127/0.098 The Malays subgroup is assumed as donor and father populations for transfusion and gestation, respectively. HPA data for Banjar, Bugis, Champa, Jawa, Kelantan, Malays, Chinese, and Indians were obtained from Wan Syafawati et al.15 and Tan et al.16 HPA = human platelet antigen; B = Batek; W = Che Wong; K = Kensiu; L = Lanoh; S = Semai; O = Orang Kanaq; BA = Banjar; BU = Bugis; C = Champa; J = Jawa; KE = Kelantan; M = Malays; CH = Chinese; I = Indians; > = donor to recipient and father to mother population for random platelet transfusion and gestation, respectively.

IMMUNOHEMATOLOGY, Volume 32, Number 4, 2016 157 W.U.W. Syafawati et al.

Table 19. Hypothetical transfusion and gestation HPA alloimmunization risks between pairs of Chinese and other Malaysian subpopulations

HPA Transfusion Gestation CH>B/W/K/L/S/O/BA/BU/C/J/KE/M/CH/I CH>B/W/K/L/S/O/BA/BU/C/J/KE/M/CH/I 1a 0/0/0.009/0/0.009/0/0/0/0/0/0/0/0/0.013 0/0/0.001/0/0.001/0/0/0/0/0/0/0/0/0.012 1b 0/0/0.075/0/0.039/0/0/0/0.038/0/0/0.047/0/0.172 0/0/0.039/0/0.012/0/0/0/0.019/0/0/0.024/0/0.090 2a 0/0/0/0/0/0/0.003/0/0.001/0/0.003/0.001/0.001/0.002 0.002/0/0/0/0/0/0.003/0/0.001/0/0.003/0/0.001/0.001 2b 0/0/0/0/0/0/0.090/0/0.054/0/0.099/0.068/0.061/0.072 0/0/0/0/0/0/0.045/0/0.027/0/0.051/0.034/0.031/0.037 3a 0.188/0.222/0.016/0.241/0.096/0.032/0.125/0.159/0.093/0.119/0.150/0.186/0.149/0.123 0.125/0.141/0.014/0.083/0.072/0.027/0.091/0.110/0.070/0.087/0.105/0.104/0.104/0.089 3b 0.188/0.147/0.179/0.241/0.248/0.221/0.235/0.213/0.248/0.239/0.220/0.189/0.220/0.238 0.125/0.103/0.096/0.148/0.148/0.122/0.145/0.137/0.148/0.147/0.140/0.126/0.140/0.146 4a 0/0/0/0/0/0/0.003/0/0/0/0/0/0/0 0/0/0/0/0/0/0/0/0/0.003/0/0/0/0 4b 0/0/0/0/0/0/0.090/0/0/0/0/0.001/0.004/0.010 0/0/0/0/0/0/0.045/0/0/0/0/0.005/0.002/0.005 5a 0.022/0.042/0.022/0/0.012/0/0.003/0.003/0/0.001/0/0.003/0/0.004 0.019/0.035/0.019/0/0.0110/0/0.003/0.003/0/0.001/0/0.003/0/0.004 5b 0.199/0.235/0.203/0/0.165/0/0.090/0.094/0.010/0.069/0/0.088/0.033/0.103 0.107/0.132/0.100/0/0.087/0/0.045/0.048/0.010/0.035/0/0.045/0.016/0.053 6a 0/0/0/0/0/0/0/0.009/0/0/0.001/0/0/0 0/0/0/0/0/0/0/0.008/0/0/0.001/0/0/0 6b 0/0/0/0/0/0/0.032/0.148/0.010/0/0.054/0.014/0.033/0.020 0/0/0/0/0/0/0.016/0.078/0.010/0/0.027/0.007/0.016/0.005 15a 0/0.188/0.242/0.248/0.175/0.008/0.182/0.123/0.197/0.212/0.150/0.180/0.188/0.288 0/0.125/0.147/0.142/0.119/0.007/0.115/0.089/0.130/0.136/0.105/0.121/0.125/0.143 15b 0/0.188/0.113/0.063/0.199/0.144/0.142/0.237/0.177/0.161/0.220/0.195/0.190/0.138 0/0.125/0.083/0.050/0.131/0.075/0.096/0.054/0.120/0.111/0.140/0.129/0.127/0.098 The Chinese subgroup is assumed as donor and father populations for transfusion and gestation, respectively. HPA data for Banjar, Bugis, Champa, Jawa, Kelantan, Malays, Chinese, and Indians were obtained from Wan Syafawati et al.15 and Tan et al.16 HPA = human platelet antigen; B = Batek; W = Che Wong; K = Kensiu; L = Lanoh; S = Semai; O = Orang Kanaq; BA = Banjar; BU = Bugis; C = Champa; J = Jawa; KE = Kelantan; M = Malays; CH = Chinese; I = Indians; > = donor to recipient and father to mother population for random platelet transfusion and gestation, respectively.

Table 20. Hypothetical transfusion and gestation HPA alloimmunization risks between pairs of Indians and other Malaysian subpopulations

HPA Transfusion Gestation I>B/W/K/L/S/O/BA/BU/C/J/KE/M/CH/I I>B/W/K/L/S/O/BA/BU/C/J/KE/M/CH/I 1a 0/0/0.009/0/0.009/0/0/0/0/0/0/0/0/0.013 0.012/00/0.001/0/0.001/0/0/0/0/0/0/0/0 1b 0/0/0.075/0/0.039/0/0/0/0.038/0/0/0.047/0/0.172 0.090/0/0/0.039/0/0.012/0/0/0/0.019/0/0/0.024/0 2a 0/0/0/0/0/0/0.003/0/0.001/0/0.003/0.001/0.001/0.002 0/0/0/0/0/0/0.003/0/0.001/0/0.003/0.001/0.001/0.002 2b 0/0/0/0/0/0/0.090/0/0.054/0/0.099/0.068/0.061/0.072 0/0/0/0/0/0/0.045/0/0.027/0/0.051/0.034/0.031/0.037 3a 0.188/0.222/0.016/0.241/0.096/0.032/0.125/0.159/0.093/0.119/0.150/0.186/0.149/0.123 0.125/0.141/0.014/0.083/0.072/0.027/0.091/0.110/0.070/0.087/0.105/0.124/0.104/0.089 3b 0.188/0.147/0.179/0.241/0.248/0.221/0.235/0.213/0.248/0.239/0.220/0.189/0.220/0.238 0.125/0.103/0.096/0.148/0.148/0.122/0.145/0.137/0.148/0.147/0.140/0.126/0.140/0.146 4a 0/0/0/0/0/0/0.003/0/0/0/0/0/0/0 0/0/0/0/0/0/0/0/0/0.003/0/0/0/0 4b 0/0/0/0/0/0/0.090/0/0/0/0/0.001/0.004/0.010 0/0/0/0/0/0/0.045/0/0/0/0/0.002/0.005/0.005 5a 0.022/0.042/0.022/0/0.012/0/0.003/0.003/0/0.001/0/0.003/0/0.004 0.019/0.035/0.019/0/0.011/0/0.003/0.003/0/0.001/0/0.003/0/0.004 5b 0.199/0.235/0.203/0/0.165/0/0.090/0.094/0.010/0.069/0/0.088/0.033/0.103 0.107/0.132/0.100/0/0.087/0/0.045/0.048/0.010/0.035/0/0.045/0.016/0.053 6a 0/0/0/0/0/0/0/0.009/0/0/0.001/0/0/0 0/0/0/0/0/0/0/0.008/0/0/0.001/0/0/0 6b 0/0/0/0/0/0/0.032/0.148/0.010/0/0.054/0.014/0.033/0.020 0/0/0/0/0/0/0.016/0.078/0.010/0/0.027/0.007/0.016/0.005 15a 0/0.188/0.242/0.248/0.175/0.008/0.182/0.123/0.197/0.212/0.150/0.180/0.188/0.288 0/0.125/0.147/0.142/0.119/0.007/0.115/0.089/0.130/0.136/0.105/0.121/0.125/0.143 15b 0/0.188/0.113/0.063/0.199/0.144/0.142/0.237/0.177/0.161/0.220/0.190/0.138/0.195 0/0.125/0.083/0.050/0.131/0.075/0.096/0.054/0.120/0.111/0.140/0.129/0.127/0.098 The Indians subgroup is assumed as donor and father populations for transfusion and gestation, respectively. HPA data for Banjar, Bugis, Champa, Jawa, Kelantan, Malays, Chinese, and Indians were obtained from Wan Syafawati et al.15 and Tan et al.16 HPA = human platelet antigen; B = Batek; W = Che Wong; K = Kensiu; L = Lanoh; S = Semai; O = Orang Kanaq; BA = Banjar; BU = Bugis; C = Champa; J = Jawa; KE = Kelantan; M = Malays; CH = Chinese; I = Indians; > = donor to recipient and father to mother population for random platelet transfusion and gestation, respectively.

158 IMMUNOHEMATOLOGY, Volume 32, Number 4, 2016 HPA diversity in Peninsular Malaysia

as the most common HPA alloantibody in a cohort of multi- 4. Stanworth SJ, Navarrete C, Estcourt L, et al. Platelet transfused thrombocytopenic patients at Universiti Sains refractoriness: practical approaches and ongoing dilemmas in patient management. Br J Haematol 2015;171:297–305. Malaysia Hospital.30 This is the second largest hospital in 5. Peterson JA, Mcfarland JG, Curtis BR, et al. Neonatal northeast Peninsular Malaysia and in 2014 supplied more than alloimmune thrombocytopenia: pathogenesis, diagnosis and 6061 units of untyped platelet concentrates/apheresis (equal management. Br J Haematol 2013;161:3–14. to more than 23 percent of total consumption of blood/blood 6. Jones DC, Bunce M, Fuggle SV, et al. Human platelet alloantigens (HPAs): PCR-SSP genotyping of a UK population components) (Z. Zefarina and M.N. Hassan, unpublished for 15 HPA alleles. Eur J Immunogenet 2003;30:415–9. data). The presence of individuals who are homozygous for 7. Bennett JA, Palmer LJ, Musk AW, et al. Gene frequencies of less frequent HPA alleles (e.g., HPA-3b/b in Batek, Che Wong, human platelet antigens 1-5 in indigenous Australians in Lanoh, Senoi, Malays, Chinese, and Indian; HPA-5b/b in Che Western Australia. Transfus Med 2002;12:199–203. 8. Sellers J, Thompson J, Guttridge MG, et al. Human platelet Wong; HPA-1b/b in Indians; HPA-2b/b in Indians; HPA- antigen: typing by PCR using sequence-specific primers and 5b/b in Indians) provides further support for our views on their distribution in blood donors resident in Wales. Eur J the significantly higher overall risk of HPA alloimmunization Immunogenet 1999;26:393–7. in Malaysia. Thus, HPA typing is expected to become an 9. Chu CC, Lee HL, Chu TW, et al. The use of genotyping to predict the phenotypes of human platelet antigens 1 through 5 and of important screening process in the future healthcare of the neutrophil antigens in Taiwan. Transfusion 2001;41:1553–8. country—especially for management of patients with PTR, 10. Shih MC, Liu TC, Lin IL, et al. Gene frequencies of the HPA-1 NAIT, and PTP. An important caveat to note is that our to HPA-13, Oe and Gov platelet antigen alleles in Taiwanese, data analysis outputs were generated from a relatively small Indonesian, Filipino and Thai populations. Int J Mol Med 2003;12:609–14. number of samples and our ancestry and health inferences 11. Kupatawintu P, Nathalang O, O-Charoen R, et al. Gene might be affected by this limitation. frequencies of the HPA-1 to 6 and Gov human platelet antigens In conclusion, we believe that the present study has in Thai blood donors. Immunohematology 2005;21:5–9. successfully genotyped HPA-1 to -6 and HPA-15 loci in Orang 12. Feng ML, Liu DZ, Shen W, et al. Establishment of an HPA-1 to -16 typed donor registry in China. Transfus Med 2006;16:369– Asli individuals in Peninsular Malaysia and shows high genetic 74. diversity related to independent waves of immigrants into this 13. Yan L, Zhu F, He J, et al. Human platelet antigen systems region in prehistoric (i.e., Semang, Senoi, and Proto-Malays) in three Chinese ethnic populations. Immunohematology and historic (Malay subethnic groups, Chinese, Indians) 2006;22:6–10. 14. De La Vega Elena CD, Nogues N, Fernandez Montoya A, times. The gene pools of the settlers in Peninsular Malaysia et al. Human platelet-specific antigens frequencies in the were then further shaped by evolutionary processes including Argentinean population. Transfus Med 2008;18:83–90. founder effects, bottlenecks, and natural selection. 15. Wan Syafawati WU, Norhalifah HK, Zefarina Z, et al. Allele frequencies of human platelet antigens in Banjar, Bugis, Champa, Jawa and Kelantan Malays in Peninsular Malaysia. Acknowledgments Transfus Med 2015;25:326–32. 16. Tan JY, Lian LH, Nadarajan VS. Genetic polymorphisms This project was supported by a short-term grant (304/ of human platelet antigens-1 to -6, and -15 in the Malaysia PPSK/61313062), and the MSc scholarship for W.U.W. population. Blood Transfus 2012;10:368–76. 17. Aghakhanian F, Yunus Y, Naidu R, et al. Unravelling the genetic Syafawati was supported by the long-term research grant history of Negritos and indigenous populations of Southeast scheme (304/PPSK/6150115/U132). G.K. Chambers thanks Asia. Genome Biol Evol 2015;7:1206–15. Victoria University of Wellington, New Zealand, for alumnus 18. Hill C, Soares P, Mormin M, et al. Phylogeography and support. ethnogenesis of aboriginal Southeast Asians. Mol Biol Evol 2006;23:2480–91. 19. Bellwood P. The origins and dispersals of agricultural References communities in Southeast Asia. In: Glover I, Bellwood P, ed. Southeast Asia: from prehistory to history. London: Routledge 1. Robinson J, Halliwell JA, McWilliam H, et al. IPD: the Immuno Curzon, 2004:21–40. Polymorphism Database. Nucleic Acids Res 2013;41:863–9. 20. Hatin WI, Nur-Shafawati AR, Etemad A, et al. A genome wide 2. Metcalfe P, Watkins NA, Ouwehand WH, et al. Nomenclature pattern of population structure and admixture in peninsular of human platelet antigens. Vox Sang 2003;85:240–5. Malaysia Malays. HUGO J 2014;8:1–18. 3. Woelke C, Eichler P, Washington G, et al. Post-transfusion 21. Xu X, Zhu F, Ying Y, et al. Simultaneous genotyping of human purpura in a patient with HPA-1a and GPIa/IIa antibodies. platelet antigen-1 to 17w by polymerase chain reaction Transfus Med 2006;16:69–72. sequence-based typing. Vox Sang 2009;97:330–7.

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22. Rodriguez S, Gaunt TR, Day INM. Hardy-Weinberg equilibrium testing of biological ascertainment for Mendelian Wan Ubaidillah Wan Syafawati, BSc, MSc student, Biomedicine randomization studies. Am J Epidemiol 2009;169:505–14. Programme, School of Health Sciences, Health Campus, Universiti 23. Halle L, Bach KH, Martageix C, et al. Eleven human platelet Sains Malaysia, Kelantan, Malaysia; Zulkafli Zefarina, M.Path, systems studied in the Vietnamese and Ma'ohis Polynesian Lecturer, Biomedicine Programme, School of Health Sciences, Health populations. Tissue Antigens 2004;63:34–40. Campus, Universiti Sains Malaysia, Kelantan, Malaysia; Zafarina 24. Edinur HA, Dunn PP, Lea RA, et al. Human platelet antigens Zafarina, PhD, Lecturer, Human Identification Unit/DNA, Forensic frequencies in Maori and Polynesian populations. Transfus Programme, School of Health Sciences, Health Campus, Universiti Med 2013;23:330–7. Sains Malaysia, Kelantan, Malaysia; Mohd Nazri Hassan, M.Path, 25. NurWaliyuddin HZA, Norazmi MN, Edinur HA, et al. Lecturer, Hematology Department, School of Medical Sciences, Ancient genetic signatures of Orang Asli revealed by killer Health Campus, Universiti Sains Malaysia, Kelantan, Malaysia, immunoglobulin-like receptor gene polymorphisms. PLoS One Mohd Nor Norazmi, PhD, Lecturer, Human Identification Unit/DNA, 2015;10:e0141536. Forensic Programme, School of Health Sciences, Health Campus, 26. Kaplan C. Foetal and neonatal alloimmune thrombocytopaenia. Universiti Sains Malaysia, Kelantan, Malaysia; Sundararajulu Orphanet J Rare Dis 2006;10:39. Panneerchelvam, MSc, Lecturer, Human Identification Unit/DNA, 27. Waters AH. Post-transfusion purpura. Blood Rev 1989;3:83–7. Forensic Programme, School of Health Sciences, Health Campus, 28. Slichter SJ, Davis K, Enright H, et al. Factors affecting Universiti Sains Malaysia, Kelantan, Malaysia; Geoffrey Keith posttransfusion platelet increments, platelet refractoriness, and platelet transfusion intervals in thrombocytopenic patients. Chambers, PhD, Lecturer, School of Biological Sciences, Victoria Blood 2005;105:4106–14. University of Wellington, Wellington, New Zealand; and Hisham 29. Armani MI, Santoso S. The relevance of platelet antigen/ Atan Edinur, PhD (corresponding author), Lecturer, Forensic antibodies in multi ethnic in Malaysia. Vox Sang 2015;109:1– Programme, School of Health Sciences, Universiti Sains Malaysia, 96. Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia, 30. Wan Mahmood WH, Mustaffa R. Platelet alloantibody in [email protected]. multiply transfused thrombocytopenic patients. Int Med J Malaysia 2007:6:1–10.

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The editorial staff of Immunohematology welcomes manuscripts submitting scientific articles, case reports, and review articles, pertaining to blood group serology and molecular genetics for see Instructions for Authors in every issue of Immunohematology consideration for publication. We are especially interested in or e-mail a request to [email protected]. Include fax and review articles, case reports, papers on platelet and white cell phone numbers and e-mail address with all manuscripts serology, scientific articles covering original investigations or new and correspondence. E-mail all manuscripts to immuno@ blood group alleles, papers on molecular testing, and papers on redcross.org. new methods for use in the blood bank. To obtain instructions for

160 IMMUNOHEMATOLOGY, Volume 32, Number 4, 2016