TY - JOUR
T1 - Nucleotide variation at Msn and Alas2, two genes flanking the centromere of the X chromosome in humans
AU - Nachman, Michael W.
AU - D'Agostino, Susan L.
AU - Tillquist, Christopher R.
AU - Mobasher, Zahra
AU - Hammer, Michael F.
PY - 2004/5
Y1 - 2004/5
N2 - The centromeric region of the X chromosome in humans experiences low rates of recombination over a considerable physical distance. In such a region, the effects of selection may extend to linked sites that are far away. To investigate the effects of this recombinational environment on patterns of nucleotide variability, we sequenced 4581 bp at Msn and 4697 bp at Alas2, two genes situated on either side of the X chromosome centromere, in a worldwide sample of 41 men, as well as in one common chimpanzee and one orangutan. To investigate patterns of linkage disequilibrium (LD) across the centromere, we also genotyped several informative sites from each gene in 120 men from sub-Saharan Africa. By studying X-linked loci in males, we were able to recover haplotypes and study long-range patterns of LD directly. Overall patterns of variability were remarkably similar at these two loci. Both loci exhibited (i) very low levels of nucleotide diversity (among the lowest seen in the human genome); (ii) a strong skew in the distribution of allele frequencies, with an excess of both very-low and very-high-frequency derived alleles in non-African populations; (iii) much less variation in the non-African than in the African samples; (iv) very high levels of population differentiation; and (v) complete LD among all sites within loci. We also observed significant LD between Msn and Alas2 in Africa, despite the fact that they, are separated by ∼10 Mb. These observations are difficult to reconcile with a simple demographic model but may be consistent with positive and/or purifying selection acting on loci within this large region of low recombination.
AB - The centromeric region of the X chromosome in humans experiences low rates of recombination over a considerable physical distance. In such a region, the effects of selection may extend to linked sites that are far away. To investigate the effects of this recombinational environment on patterns of nucleotide variability, we sequenced 4581 bp at Msn and 4697 bp at Alas2, two genes situated on either side of the X chromosome centromere, in a worldwide sample of 41 men, as well as in one common chimpanzee and one orangutan. To investigate patterns of linkage disequilibrium (LD) across the centromere, we also genotyped several informative sites from each gene in 120 men from sub-Saharan Africa. By studying X-linked loci in males, we were able to recover haplotypes and study long-range patterns of LD directly. Overall patterns of variability were remarkably similar at these two loci. Both loci exhibited (i) very low levels of nucleotide diversity (among the lowest seen in the human genome); (ii) a strong skew in the distribution of allele frequencies, with an excess of both very-low and very-high-frequency derived alleles in non-African populations; (iii) much less variation in the non-African than in the African samples; (iv) very high levels of population differentiation; and (v) complete LD among all sites within loci. We also observed significant LD between Msn and Alas2 in Africa, despite the fact that they, are separated by ∼10 Mb. These observations are difficult to reconcile with a simple demographic model but may be consistent with positive and/or purifying selection acting on loci within this large region of low recombination.
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U2 - 10.1534/genetics.167.1.423
DO - 10.1534/genetics.167.1.423
M3 - Article
C2 - 15166166
SN - 0016-6731
VL - 167
SP - 423
EP - 437
JO - Genetics
JF - Genetics
IS - 1
ER -