Further Observations on Kell Blood Groups in Families Ascertained Via a Mongol Propositus D

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Further Observations on Kell Blood Groups in Families Ascertained Via a Mongol Propositus D J Med Genet: first published as 10.1136/jmg.5.4.310 on 1 December 1968. Downloaded from J. med. Genet. (1968). 5, 310. Further Observations on Kell Blood Groups in Families Ascertained via a Mongol Propositus D. A. PRICE EVANS, P. J. J. WREN, W. T. A. DONOHOE, M. F. BULLEN, MARION LEWIS, HIROKO KAITA, BRUCE CHOWN, and IRENE UCHIDA From Nuffield Unit of Medical Genetics, Department of Medicine, University of Liverpool, Liverpool, U.K.; and Rh Laboratory and Department of Paediatrics, University of Manitoba, Winnipeg, Canada Genes located on the unpaired portion of the cal significance level of a result on a single system human X chromosome can readily be recognized, but would have to be weighted appropriately, and that as far as the autosomes are concerned it is not known the ideal confirmatory procedure would be to ana- upon which autosome any human gene is located. lyse statistically only the Kell blood grouping results The common variety of mongolism is charac- from an entirely new population of mongols and terized by 21-trisomy, and offers a possible approach their sibs. to the localization of human autosomal genes. The The present paper presents the results of such a model on which this approach is based was first confirmatory procedure. formulated by Bateman (1960) and later developed by Shaw and Gershowitz (1962), Penrose (1963), Materials and Methods Kaplan et al. (1964), and Goodman (1965). The The studies were carried out independently in Liver- essential experimental finding would be a reduced pool and Winnipeg. Where the methods were differentcopyright. incidence of a recessive phenotype or homozygous this is stated. genotype in the 21 trisomics as compared with non- trisomics, which would indicate that the genes con- Subjects. Mongol propositi were located in the trolling the polymorphism involved were located on following ways: chromosome 21. Results (i) In England from the general practice list of one of testing the ABO blood us (P.J.J.W.) and his partners at Chorley; from'investi- group system were published by Shaw and gations at Lisieux Hall Mental Institution, Whittle-le- Gershowitz (1962, 1963), Chown and Lewis (1963), Woods, near Chorley, Lancashire, and from lists sup- http://jmg.bmj.com/ Kaplan et al. (1964), and Goodman and Thomas plied by the Medical Officers of Health of Chorley, (1966). From these results it seems very unlikely Birkenhead, and S.W. Lancashire, all of whom have that the ABO locus is on autosome 21. responsibilities for providing educational facilities for Evans et al. (1966) analysed data collected in mentally backward children. Liverpool, in Buffalo, New York, U.S.A., and from (ii) In Manitoba from investigations at the Manitoba a London series in the paper of Lang-Brown, School for Retardates; or through a list supplied by the Lawler, and Penrose school; or through reference by private physicians or the (1952/53). Data on nine Public Health Service. An attempt was made to see, on September 26, 2021 by guest. Protected blood group systems and salivary ABH secretion examine, and test every mongol in Manitoba (population were analysed. The only significant association 1,000,000). between blood group phenotype and mongolism was found in the case of Kell where a significant ex- Diagnosis of Mongolism. All Manitoba mongols cess of Kell-positive mongols was found. This were seen by one of us (I.U.) as part of her study of finding raised the possibility that the Kell locus mongolism. The diagnosis was made on clinical might be on chromosome 21. grounds and was confirmed by dermatoglyphs and by Objections to concluding that the human Kell karyotypes. Only trisomics and their relatives, and locus was on only families in which at least the mongol and both chromosome 21 were discussed. parents had been blood grouped, have been analysed in Among others it was pointed out that since a number this paper. ofpolymorphisms had been investigated the statisti- The diagnosis of the British mongols was a purely clinical one. Mongol propositi were not accepted unless they had typical physiognomic features. Karyotyping facilities were not available in Liverpool for the large Received May 6, 1968. number of subjects involved. 310 J Med Genet: first published as 10.1136/jmg.5.4.310 on 1 December 1968. Downloaded from Further Observations on Kell Blood Groups in Famlies Ascertained via a Mongol Propositus 311 TABLE I MANITOBA FAMILIES ASCERTAINED VIA A TRISOMIC PROPOSITUS Families which have AllMembersof Families members not T % Kell Kell Typing K-k+ Kp(a-b+) K-k+ Kp(a-b+) otal Positive kbkb kakb Kkb KK Male mongols 112 10 1 8 Nil 131 6-87 682 Female mongols 110 14 2 7 Nil 133 6-77 f Fathers of mongols 215 16 2 24 Nil 257 10-12L 8 37 Mothers of mongols 215 25 5 12 Nil 257 6-61 r Brothers of mongols 289 22 6 30 Nil 347 10-37 880 Sisters of mongols 258 32 1 20 1 312 7-05 8 Note: For the purpose of this analysis ke is taken as equivalent to K. There were three sets of monozygous female mongols; they were each counted as one. There were also two non-mongol sibs whose sex was not recorded; they have been omitted. Relatives of Mongol Propositi. All available sibs anti-K antiserum within 36 hours of collection. Typ- and the parents were ascertained for the Manitoba ing with anti-k antiserum was not regularly performed. mongols. In the British mongols a non-mongol sib was ascer- Antisera. The sera of the Kell system used in the tained along with each mongol propositus. Mongols Manitoba study and the methods by which they were without an available non-mongol sib were not investi- used were the same as described by Chown et al. (1963), gated. Wherever possible.the non-mongol sib nearest save that latterly the anti-Kpb has been used by the indi- in age to the mongol propositus and the parents of the rect Coombs technique. All samples were tested with propositi were examined. anti-K, -k, -Kpa, and-Kpb. Later in the study all available non-mongol sibs were The British blood samples w itedi ortho. ascertained in families where one or other of the parents immune specific anti-Kell (an vby indirect of B1itish mongols had bees shown to possess the Kell Coombs test only. No other dpoOpp* systems antigen. were tested. copyright. Control Families. In England a control non- Method of C. A. B. Smith foi Evaluating Asso- mongol matched propositus was selected from the ciations within Families. This method utilizes segre- general practice list at Chorley already indicated. gating sibships, and is fully explained in the paper of Each mongol propositus in the Chorley series was Clarke et al. (1956) where it was first used to test the matched by a control non-mongol propositus ofthe same association between blood group 0 and duodenal ulcer sex, age, socio-economic status, location of domicile, and within sibships. cultural background. A non-mongol sib, and wherever possible, the parents of the control non-mongol matched http://jmg.bmj.com/ propositus were also investigated in the same manner as Results for mongol propositi. Manitoba families are analysed in Table I, and it will be seen that the frequency of the Kell antigen is Blood Samples. The Manitoba samples were not higher in the trisomics than in their parents or collected from 1962 to November 1967. All were sibs. venous samples. They were collected in mental insti- Data on British families of phenotypically tutions, in hospitals, in the genetics laboratory, and in charac- the homes of propositi or their relatives, and were de- teristic mongols and on families of controls are on September 26, 2021 by guest. Protected livered as soon as convenient to the Rh Laboratory. All presented in Tables II and III, respectively. were typed for the ABO, MNSs, Rh, P, Kell, Lutheran, Table IV shows data from Chorley families. The Lewis, Duffy, Kidd, and Xg systems, many for the frequency of Kell-positive is not higher in the Bua-Sm system, and for a variety of high and low mongols than in their parents or sibs. The fre- frequency antigens. The facts so obtained were used to quency of Kell-positive is not higher in mongols check paternity, but only the Kell data were statistically than in control non-mongol matched propositi. It analysed in the present study. is also clear than the matings which give rise to The British blood samples were taken by venepuncture mongols do not have a different from almost all subjects. Blood from a few uncoopera- incidence of Kell- tive mongol subjects was obtained by ear-prick. The positive from those which have produced control blood samples taken at Chorley were sent by overnight non-mongol propositi. letter post to the blood grouping laboratory in Liverpool The frequency of Kell positive in the parents of and the samples taken in Birkenhead and South West Manitoba trisomics and in the parents of the British Lancashire were taken there immediately. All British phenotypically characteristic mongols is seen to be blood samples were typed for their Kell blood group with similar in Table V. J Med Genet: first published as 10.1136/jmg.5.4.310 on 1 December 1968. Downloaded from 312 Evans, Wren, Donohoe, Bullen, Lewis, Kaita, Chown, and Uchida TABLE II Conclusion KELL TYPING INFORMATION ON BRITISH FAMILIES The data contained in the no ASCERTAINED BY MEANS OF PHENOTYPICALLY present report lend CHARACTERISTIC MONGOL PROPOSITUS support to the tentative suggestion made earlier by Evans et al. (1966) that the Kell locus may be on Area from Which Family S No.
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