Genetic Diversity of HLA System in Two Populations from Durango, Mexico: Durango City and Rural Durango

Genetic diversity of HLA system in two populations from Durango, Mexico: Durango City and rural Durango.

Liliana González-Medina*, Héctor Delgado-Aguirre*, Rodrigo Barquera*‡, Stephen Clayton*, Carmen Adalid-Sáinz*, Esteban Arrieta-Bolaños*, Hanna Pacheco-Ubaldo, Diana Iraíz Hernández-Zaragoza, Néstor Escareño-Montiel, Javier Morán-Martínez, Alicia Bravo-Acevedo, Abraham Lona-Sánchez, Marisela del Rocío González-Martínez, Yolanda Jaramillo-Rodríguez, Antonio Salgado-Adame, Federico Juárez-de la Cruz, Joaquín Zúñiga‡, Edmond J. Yunis, Carolina Bekker-Méndez, Julio Granados.

* These authors contributed equally to the present work.

‡ Addresses for correspondence: Rodrigo Barquera: [email protected]; Joaquín Zúñiga: [email protected].

Supplementary information

Supplementary Table 1: HLA-A allelic frequencies from the state of Durango: Mexico Durango, Durango city (AFND-ID: 3516) and Mexico Durango Rural (AFND-ID: 3575)...... 2 Supplementary Table 2: HLA-B allelic frequencies from the state of Durango: Mexico Durango, Durango city (AFND-ID: 3516) and Mexico Durango Rural (AFND-ID: 3575)...... 3 Supplementary Table 3: HLA-DRB1 allelic frequencies from the state of Durango: Mexico Durango, Durango city (AFND-ID: 3516) and Mexico Durango Rural (AFND-ID: 3575)...... 4 Supplementary Table 4: HLA-DQB1 allelic frequencies from the state of Durango: Mexico Durango, Durango city (AFND-ID: 3516) and Mexico Durango Rural (AFND-ID: 3575)...... 5 Supplementary Table 5: HLA-A~B~DRB1~DQB1 haplotypes from the state of Durango...... 6 Supplementary Table 6: HLA-A~B~DRB1~DQB1 haplotypes from Mexico Durango, Durango city (AFND-ID: 3516)...... 7 Supplementary Table 7: HLA-A~B~DRB1~DQB1 haplotypes from Mexico Durango Rural (AFND-ID: 3575)...... 8 Supplementary Table 8: Hardy-Weinberg equilibrium (HWE) parameters for the sample sets from Durango...... 9

Supplementary Table 1: HLA-A allelic frequencies from the state of Durango: Mexico Durango, Durango city (AFND-ID: 3516) and Mexico Durango Rural (AFND-ID: 3575).

Durango Durango city Durango Rural Allele (N=479) (N=153) A.F. (N=326) A.F. A*01 0.0965 0.0935 0.0979 A*02 0.2863 0.2419 0.3073 A*03 0.0415 0.0548 0.0352 A*11 0.0477 0.0742 0.0352 A*23 0.0218 0.0161 0.0245 A*24 0.1743 0.1871 0.1682 A*25 0.0052 0.0032 0.0061 A*26 0.0270 0.0323 0.0245 A*29 0.0394 0.0258 0.0459 A*30 0.0425 0.0419 0.0428 A*31 0.0622 0.0839 0.0520 A*32 0.0187 0.0226 0.0168 A*33 0.0176 0.0161 0.0183 A*34 0.0031 0.0032 0.0031 A*43 0.0010 0.0000 0.0015 A*66 0.0093 0.0000 0.0138 A*68 0.0996 0.1000 0.0994 A*69 0.0031 0.0000 0.0046 A*74 0.0010 0.0000 0.0015 A*80 0.0010 0.0000 0.0015

A.F.: Allelic frequency. N refers to the number of individuals analyzed.

Supplementary Table 2: HLA-B allelic frequencies from the state of Durango: Mexico Durango, Durango city (AFND-ID: 3516) and Mexico Durango Rural (AFND-ID: 3575).

Durango Durango city Durango Rural Allele (N=479) (N=153) A.F. (N=326) A.F. B*07 0.0436 0.0452 0.0428 B*08 0.0571 0.0452 0.0627 B*13 0.0104 0.0129 0.0092 B*14:01 0.0083 0.0097 0.0076 B*14:02 0.0270 0.0323 0.0245 B*15:01 0.0425 0.0323 0.0474 B*15:02 0.0010 0.0000 0.0015 B*15:03 0.0062 0.0032 0.0076 B*15:05 0.0021 0.0000 0.0031 B*15:09 0.0041 0.0032 0.0046 B*15:10 0.0062 0.0000 0.0092 B*15:15 0.0031 0.0065 0.0015 B*15:16 0.0031 0.0000 0.0046 B*15:17 0.0062 0.0097 0.0046 B*15:56 0.0010 0.0000 0.0015 B*18 0.0373 0.0290 0.0413 B*27 0.0176 0.0290 0.0122 B*35 0.1701 0.2000 0.1560 B*37 0.0052 0.0000 0.0076 B*38 0.0104 0.0097 0.0107 B*39 0.0954 0.0774 0.1040 B*40:01 0.0083 0.0065 0.0092 B*40:02 0.0934 0.1065 0.0872 B*40:05 0.0197 0.0226 0.0183 B*40:08 0.0052 0.0032 0.0061 B*41 0.0166 0.0161 0.0168 B*42 0.0041 0.0097 0.0015 B*44 0.0820 0.0710 0.0872 B*45 0.0145 0.0065 0.0183 B*47 0.0041 0.0065 0.0031 B*48 0.0228 0.0452 0.0122 B*49 0.0249 0.0355 0.0199 B*50 0.0073 0.0065 0.0076 B*51 0.0477 0.0613 0.0413 B*52 0.0363 0.0290 0.0398 B*53 0.0124 0.0129 0.0122 B*55 0.0083 0.0000 0.0122 B*56 0.0010 0.0032 0.0000 B*57 0.0176 0.0032 0.0245 B*58 0.0093 0.0065 0.0107 B*78 0.0010 0.0000 0.0015

A.F.: Allelic frequency. N refers to the number of individuals analyzed.

Supplementary Table 3: HLA-DRB1 allelic frequencies from the state of Durango: Mexico Durango, Durango city (AFND-ID: 3516) and Mexico Durango Rural (AFND-ID: 3575).

Durango Durango city Durango Rural Allele (N=479) (N=153) A.F. (N=326) A.F. DRB1*01 0.0539 0.0484 0.0566 DRB1*01:03 0.0073 0.0065 0.0076 DRB1*03:01 0.0757 0.0548 0.0856 DRB1*03:02 0.0021 0.0032 0.0015 DRB1*04 0.3019 0.3226 0.2920 DRB1*07 0.0654 0.0581 0.0688 DRB1*08 0.1027 0.1323 0.0887 DRB1*09 0.0093 0.0129 0.0076 DRB1*10 0.0114 0.0129 0.0107 DRB1*11 0.0975 0.0935 0.0994 DRB1*12 0.0062 0.0000 0.0092 DRB1*13 0.0788 0.0516 0.0917 DRB1*14 0.0923 0.0935 0.0917 DRB1*15 0.0529 0.0581 0.0505 DRB1*16 0.0425 0.0516 0.0382

A.F.: Allelic frequency. N refers to the number of individuals analyzed.

Supplementary Table 4: HLA-DQB1 allelic frequencies from the state of Durango: Mexico Durango, Durango city (AFND-ID: 3516) and Mexico Durango Rural (AFND-ID: 3575).

Durango Durango city Durango Rural Allele (N=479) (N=153) A.F. (N=326) A.F. DQB1*02 0.1421 0.1194 0.1529 DQB1*03:01 0.2293 0.2129 0.2370 DQB1*03:02 0.2853 0.3129 0.2722 DQB1*03:03 0.0124 0.0097 0.0138 DQB1*04 0.1100 0.1419 0.0948 DQB1*05 0.0996 0.1032 0.0979 DQB1*06 0.1214 0.1000 0.1315

A.F.: Allelic frequency. N refers to the number of individuals analyzed.

Supplementary Table 5: HLA-A~B~DRB1~DQB1 haplotypes from the state of Durango.

Haplotype n= (2N=958) H.F. Δ' t A*02~B*35~DRB1*04~DQB1*03:02 22 2.30 0.1884 3.5 A*01~B*08~DRB1*03:01~DQB1*02 21 2.20 0.7017 9.1 A*02~B*40:02~DRB1*04~DQB1*03:02 20 2.09 0.4287 5.9 A*68~B*39~DRB1*04~DQB1*03:02 18 1.88 0.8018 7.8 A*02~B*39~DRB1*04~DQB1*03:02 17 1.78 0.4861 5.9 A*29~B*44~DRB1*07~DQB1*02 14 1.46 0.5087 7.2 A*02~B*15:01~DRB1*04~DQB1*03:02 12 1.26 0.3693 4.2 A*02~B*35~DRB1*08~DQB1*04 12 1.26 0.1401 4.2 A*24~B*35~DRB1*04~DQB1*03:02 12 1.26 0.2219 5.1 A*24~B*35~DRB1*08~DQB1*04 11 1.15 -0.0154 -0.1 A*24~B*39~DRB1*04~DQB1*03:02 11 1.15 0.1212 1.7 A*24~B*39~DRB1*14~DQB1*03:01 11 1.15 0.3143 5.8 A*24~B*40:02~DRB1*04~DQB1*03:02 11 1.15 0.3100 5.4 A*24~B*40:02~DRB1*08~DQB1*04 11 1.15 0.1388 1.9 A*68~B*40:02~DRB1*04~DQB1*03:02 10 1.05 0.6798 5.3

Supplementary Table 6: HLA-A~B~DRB1~DQB1 haplotypes from Mexico Durango, Durango city (AFND-ID: 3516).

Haplotype n= (2N=306) H.F. Δ' t A*02~B*40:02~DRB1*04~DQB1*03:02 9 2.90 0.7363 5.2 A*68~B*39~DRB1*04~DQB1*03:02 9 2.90 0.8550 5.7 A*24~B*35~DRB1*04~DQB1*03:02 6 2.26 -0.0337 -0.2 A*24~B*40:02~DRB1*08~DQB1*04 6 1.94 0.4226 4.2 A*02~B*35~DRB1*04~DQB1*03:02 5 1.61 0.0030 0.0 A*02~B*35~DRB1*08~DQB1*04 5 1.61 0.2061 2.9 A*02~B*48~DRB1*04~DQB1*03:02 5 1.61 0.4562 2.9 A*24~B*40:02~DRB1*04~DQB1*03:02 5 1.61 0.1540 1.3 A*02~B*44~DRB1*04~DQB1*03:02 4 1.29 0.3785 2.3 A*11~B*14:02~DRB1*01~DQB1*05 4 1.29 1.0000 4.1 A*24~B*35~DRB1*08~DQB1*04 4 1.29 0.0762 1.4 A*30~B*13~DRB1*07~DQB1*02 4 1.29 1.0000 4.1 A*68~B*48~DRB1*04~DQB1*03:02 4 1.29 0.7100 3.4

H.F.: Haplotypic frequency. Δ’: Standardized linkage disequilibrium. t: validation statistic parameter; t values > 2 were taken as significant. N refers to the number of individuals analyzed. Native American MPA haplotypes are shadowed in purple, European MPA haplotypes in green and Asian MPA haplotypes in red. Only haplotypes with H.F. ≥ 1.0% are included in this table. The whole list of haplotypes and individual genotypes for this population can be found at The Allele Frequency Net Database website (www.allelefrequencies.net).

Supplementary Table 7: HLA-A~B~DRB1~DQB1 haplotypes from Mexico Durango Rural (AFND-ID: 3575).

Haplotype n= (2N=652) H.F. Δ' t A*01~B*08~DRB1*03:01~DQB1*02 18 2.75 0.7263 8.5 A*02~B*35~DRB1*04~DQB1*03:02 17 2.60 0.2837 4.4 A*02~B*39~DRB1*04~DQB1*03:02 14 2.14 0.4689 5.4 A*29~B*44~DRB1*07~DQB1*02 13 1.99 0.4875 7.0 A*02~B*40:02~DRB1*04~DQB1*03:02 11 1.68 0.2919 3.6 A*02~B*15:01~DRB1*04~DQB1*03:02 10 1.53 0.4911 4.6 A*24~B*39~DRB1*14~DQB1*03:01 10 1.53 0.3464 5.6 A*68~B*39~DRB1*04~DQB1*03:02 10 1.53 0.1314 1.8 A*24~B*39~DRB1*04~DQB1*03:02 9 1.38 0.7532 5.4 A*02~B*18~DRB1*03:01~DQB1*02 8 1.22 0.5308 5.3 A*24~B*35~DRB1*08~DQB1*04 8 1.22 0.3442 4.9 A*02~B*35~DRB1*08~DQB1*04 7 1.07 0.1195 3.2 A*02~B*52~DRB1*04~DQB1*03:02 7 1.07 0.3736 3.3 A*68~B*40:02~DRB1*04~DQB1*03:02 7 1.07 0.8304 4.9

H.F.: Haplotypic frequency. Δ’: Standardized linkage disequilibrium. t: validation statistic parameter; t values > 2 were taken as significant. N refers to the number of individuals analyzed. Native American MPA haplotypes are shadowed in purple and European MPA haplotypes in green. Only haplotypes with H.F. ≥ 1.0% are included in this table. The whole list of haplotypes and individual genotypes for this population can be found at The Allele Frequency Net Database website (www.allelefrequencies.net).

Supplementary Table 8: Hardy-Weinberg equilibrium (HWE) parameters for the sample sets from Durango.

Population HLA-A HLA-B HLA-DRB1 HLA-DQB1

Obs.Het. 0.8631 0.9357 0.8693 0.8278

Durango Exp.Het. 0.8561 0.9312 0.8571 0.8098

p-value 0.4719 0.1604 0.2084 0.6147

Obs.Het. 0.8581 0.9355 0.8387 0.8065 Durango city Exp.Het. 0.8705 0.9231 0.8459 0.8042 (AFND-ID: 3516) p-value 0.1193 0.1759 0.3816 0.6356

Obs.Het. 0.8654 0.9358 0.8838 0.8379 Durango Rural Exp.Het. 0.8479 0.9341 0.8619 0.8116 (AFND-ID: 3575) p-value 0.8069 0.1571 0.1097 0.6716

Obs. Het.: Observed heterozygosity. Exp. Het.: Expected heterozygosity under HWE conditions; p-value refers to that of the difference between observed and expected heterozygosity values. Only p-values below 0.0125 (after correction) are considered as significant (shaded in yellow). AFND-ID: Allele Frequencies Net Database Identifier. Rows in bold indicate that the data refers to the whole state which is the sum of individual genotypes of each population present in the state.