AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY 85:329-334 (19911
Population Variation in Molecular Polymorphisms of the Short Arm of the Human X Chromosome S.S.PAF'IHA, S.S. MASTANA, D.F. ROBERTS, G.C. ONYEMELUKWE, AND S.S.BHATTACHARYA
Department of Human Genetics, University of Newcastle u on Tyne, Newcastle upon Tyne NE2 4AA, England (S.S.P.,D.F.R., {S.B.); Immunology Unit, Department of Medicine, Ahmadu Bella University Hospital, Zaria, Nigeria (G.C.O.)
KEY WORDS ABSTRACT Five DNA probes (RC8, 754, X J 1-1,pert 87.8, and L1.28) from the short arm of the human X chromosome were investigated in samples from five populations (English, Nigerian, Chinese, Muslim, and Hindu from India). The variation in the allele frequencies of several probes between different groups was significant. The average heterozygosity in females of the five populations ranged from 32% to 51%. The genetic distance between the five groups was compatible with that using traditional polymorphic systems. There is an interesting suggestion of longitudinal cline for allele "2 (9 kb) detected with probe L1.28. The X-linked RFLPs are useful genetic markers for anthropological studies. Serological and biochemical polymorphisms have been extensively used to understand the phylogenetic relationships and the genetic structure of various human opulations. In the last decade the search or new enzyme/protein pol morphisms has made little advance, main y because of the limitation of the technique of electrophoresis t o differentiating only variation that accompanies a net change in the charge of the protein molecule. However, the same techni ue has com letely transformed the study of uman DNL! polymorphisms, electro horesis being ap lied to separate the smal fragments of dif ferent sizes that result after treatment with enzymes (restriction endonucleases) t o cleave the total genomic DNA. The mutations that alter the nucleotide sequences, both coding and noncodin sequences, vide fragments of DNA of ifferent lengt in polymorphic frequencies (Botstein et al., 1980). Several hundreds of these restriction fragment length polymorphisms (RFLPs) are now known, widely distributed in the human enome, and provide a powerful means o carrier detection and prenatal diagnosis of various inherited diseases with unidentified biochemical lesions (Hofker et al., 1985). Clinically the short arm of the human X
f!
T
P
cf
B
@ 1991 WILEY-LISS. INC
R
chromosome is of great interest. Several highly polymorphic DNA probes localised there have been isolated from genomic, Xchromosome-sorted, and hybrid cell line libraries (Willard et al., 1985; Wieacker et al., 1984). These DNA olymorphisms have helped to map man zlinked diseases such as ichthyosis, Duc ennemecker muscular
7l
probes in healthy populations. There is no conclusive heterogeneity in frequency of any of these probes in European populations, except for the 5.3 kb allele identified by RC8 probe (Schurmann et al., 1987).However, for some of these probes, there are much wider differences in fre uency in different races (Summers, 1987; apiha et al., 1988; Wadhwa et al., 1989).Recent investigations with DNA probes from the short arm of the X chromosome linked t o the Duchenne muscular dystrophy gene have shown significant variation among populations in different continents, suggesting that it is important to
Y-
3
Received November 20,1989; accepted November 30, 1990. S.S. Mastana is now at Department of Human Sciences, Loughborough University of Technology, Loughborough, England.
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S.S.PAPIHA ET AL
TABLE I . Allele frequencies of DNA polymorphisms for 754, X J l - I , 87.8, L.1.28, a n d RC8 in five population groups European (Northeast England)
Probe and allele 754 (DXS84) *1 (12 kb) *2 (9 kb) XJ1-l (DXS206) *1 (3.8 kb) *2 (3.1 kb) Pert 87.8 (DXS164) *I (3.8 kb) *2 (1.1 and 2.7 kb) L.1.28 (DXS7) *I (12 kb) "2 (9 kb) RC8 (DXS9) * I (3.2 kb) *2 (5.3 kb) *3 (3.0 kb)
(172)' 0.593 f 0.0372 0.407 (139) 0.252 0.748
+ 0.037
(150) 0.280 0.720
+ 0.037
(20) 0.318 f 0.104 0.682 (28) 0.857 0.066 0.143 (28) 0.214 f 0.078 0.786 (26) 0.538 0.098 0.462 (45) 0.560 f 0.074 0.440
(110) 0.773 f 0.040 0.227
*
5.1 9.9 16.9 16.5 3.6 25.1
(62) 0.806 0.194
*
(41) 0.875 f 0.052 0.115 0.050 0.010 f 0.016 754 x2 P
Population Variation in Molecular Polymorphisms of the Short Arm of the Human X Chromosome S.S.PAF'IHA, S.S. MASTANA, D.F. ROBERTS, G.C. ONYEMELUKWE, AND S.S.BHATTACHARYA
Department of Human Genetics, University of Newcastle u on Tyne, Newcastle upon Tyne NE2 4AA, England (S.S.P.,D.F.R., {S.B.); Immunology Unit, Department of Medicine, Ahmadu Bella University Hospital, Zaria, Nigeria (G.C.O.)
KEY WORDS ABSTRACT Five DNA probes (RC8, 754, X J 1-1,pert 87.8, and L1.28) from the short arm of the human X chromosome were investigated in samples from five populations (English, Nigerian, Chinese, Muslim, and Hindu from India). The variation in the allele frequencies of several probes between different groups was significant. The average heterozygosity in females of the five populations ranged from 32% to 51%. The genetic distance between the five groups was compatible with that using traditional polymorphic systems. There is an interesting suggestion of longitudinal cline for allele "2 (9 kb) detected with probe L1.28. The X-linked RFLPs are useful genetic markers for anthropological studies. Serological and biochemical polymorphisms have been extensively used to understand the phylogenetic relationships and the genetic structure of various human opulations. In the last decade the search or new enzyme/protein pol morphisms has made little advance, main y because of the limitation of the technique of electrophoresis t o differentiating only variation that accompanies a net change in the charge of the protein molecule. However, the same techni ue has com letely transformed the study of uman DNL! polymorphisms, electro horesis being ap lied to separate the smal fragments of dif ferent sizes that result after treatment with enzymes (restriction endonucleases) t o cleave the total genomic DNA. The mutations that alter the nucleotide sequences, both coding and noncodin sequences, vide fragments of DNA of ifferent lengt in polymorphic frequencies (Botstein et al., 1980). Several hundreds of these restriction fragment length polymorphisms (RFLPs) are now known, widely distributed in the human enome, and provide a powerful means o carrier detection and prenatal diagnosis of various inherited diseases with unidentified biochemical lesions (Hofker et al., 1985). Clinically the short arm of the human X
f!
T
P
cf
B
@ 1991 WILEY-LISS. INC
R
chromosome is of great interest. Several highly polymorphic DNA probes localised there have been isolated from genomic, Xchromosome-sorted, and hybrid cell line libraries (Willard et al., 1985; Wieacker et al., 1984). These DNA olymorphisms have helped to map man zlinked diseases such as ichthyosis, Duc ennemecker muscular
7l
probes in healthy populations. There is no conclusive heterogeneity in frequency of any of these probes in European populations, except for the 5.3 kb allele identified by RC8 probe (Schurmann et al., 1987).However, for some of these probes, there are much wider differences in fre uency in different races (Summers, 1987; apiha et al., 1988; Wadhwa et al., 1989).Recent investigations with DNA probes from the short arm of the X chromosome linked t o the Duchenne muscular dystrophy gene have shown significant variation among populations in different continents, suggesting that it is important to
Y-
3
Received November 20,1989; accepted November 30, 1990. S.S. Mastana is now at Department of Human Sciences, Loughborough University of Technology, Loughborough, England.
330
S.S.PAPIHA ET AL
TABLE I . Allele frequencies of DNA polymorphisms for 754, X J l - I , 87.8, L.1.28, a n d RC8 in five population groups European (Northeast England)
Probe and allele 754 (DXS84) *1 (12 kb) *2 (9 kb) XJ1-l (DXS206) *1 (3.8 kb) *2 (3.1 kb) Pert 87.8 (DXS164) *I (3.8 kb) *2 (1.1 and 2.7 kb) L.1.28 (DXS7) *I (12 kb) "2 (9 kb) RC8 (DXS9) * I (3.2 kb) *2 (5.3 kb) *3 (3.0 kb)
(172)' 0.593 f 0.0372 0.407 (139) 0.252 0.748
+ 0.037
(150) 0.280 0.720
+ 0.037
(20) 0.318 f 0.104 0.682 (28) 0.857 0.066 0.143 (28) 0.214 f 0.078 0.786 (26) 0.538 0.098 0.462 (45) 0.560 f 0.074 0.440
(110) 0.773 f 0.040 0.227
*
5.1 9.9 16.9 16.5 3.6 25.1
(62) 0.806 0.194
*
(41) 0.875 f 0.052 0.115 0.050 0.010 f 0.016 754 x2 P
