Genomic Scans of Zygotic Disequilibrium and Epistatic SNPs in HapMap Phase III Populations

Abstract

Previous theory indicates that zygotic linkage disequilibrium (LD) is more informative than gametic or composite digenic LD in revealing natural population history. Further, the difference between the composite digenic and maximum zygotic LDs can be used to detect epistatic selection for fitness. Here we corroborate the theory by investigating genome-wide zygotic LDs in HapMap phase III human populations. Results show that non-Africa populations have much more significant zygotic LDs than do Africa populations. Africa populations (ASW, LWK, MKK, and YRI) possess more significant zygotic LDs for the double-homozygotes (DAABB) than any other significant zygotic LDs (DAABb, DAaBB, and DAaBb), while non-Africa populations generally have more significant DAaBb’s than any other significant zygotic LDs (DAABB, DAABb, and DAaBB). Average r-squares for any significant zygotic LDs increase generally in an order of populations YRI, MKK, CEU, CHB, LWK, JPT, CHD, TSI, GIH, ASW, and MEX. Average r-squares are greater for DAABB and DAaBb than for DAaBB and DAABb in each population. YRI and MKK can be separated from LWK and ASW in terms of the pattern of average r-squares. All population divergences in zygotic LDs can be interpreted with the model of Out of Africa for modern human origins. We have also detected 19735-95921 SNP pairs exhibiting strong signals of epistatic selection in different populations. Gene-gene interactions for some epistatic SNP pairs are evident from empirical findings, but many more epistatic SNP pairs await evidence. Common epistatic SNP pairs rarely exist among all populations, but exist in distinct regions (Africa, Europe, and East Asia), which helps to understand geographical genomic medicine.

High mutation rates explain low population genetic divergence at copy-number-variable loci in Homo sapiens

“…Evidence at genome-wide CNV loci supports the hypothesis that CHB and CHD have a very close genetic relationship. This is slightly different from the genetic relationships revealed by the patterns of zygotic and gametic LDs at the genome-wide SNP sites where JPT and CHD have a very close genetic relationship 37 . Genetic drift effects could explain the relative small differentiation in polymorphism at CNV loci in Asian and European populations.…”

“…Epistasis does not exist for any pair of CNV loci, presuming that these CNV loci are not selectively neutral or equally additive in influencing fitness. This result is different from those at the genome-wide SNP sites where epistasis occurs among many intron SNPs 37 . The results provide additional support for a recent report indicating that the 856 CNV loci are selectively neutral in each population 23 .…”

“…The difference between the values of gametic LD and maximum zygotic LD can be used to infer whether epistasis exists between loci. Such differences tested previously at the genome-wide SNP sites with the HapMap Phase III populations 37 , have shown the existence of epistases among many SNP sites. Here, we also investigate this property at the genome-wide CNV loci by presuming that individual CNV loci are directly/indirectly or equally involved in fitness changes.…”

“…To further address the population genetic properties of CNV loci and reinforce our explanations of evolution at CNV loci, we test LDs at both gametic and zygotic levels among all pairs of CNV loci. We compare the patterns of gametic and zygotic LDs at CNV loci with those previously reported at SNP sites 36 37 . Recent theoretical studies indicate that zygotic LD is more informative than gametic LD for inferring the effects of different evolutionary forces (mating system, gene flow, selection, and genetic drift) 38 39 .…”

Comparison of Genetic Variants in Cancer-Related Genes between Chinese Hui and Han Populations

“…Genotyping data from six 1000 Genomes Project population samples (99 Utah residents with northern and western European ancestry (CEU), 107 Toscani in Italy (TSI), 108 Yoruba in Ibadan (YRI), 61 persons of African ancestry in the southwestern United States (ASW), 103 Han Chinese in Beijing (CHB), and 104 Japanese in Tokyo (JPT)) were included in this study. According to two references by Xu et al and Hu et al, we downloaded the genotype data of individuals from six populations from the 1000 Genomes Project web site ( www.1000genomes.org ) as controls [ 20 , 21 ]. These individuals derive from three different population groups covering six subpopulations: CEU and TSI as European groups, YRI as representation of Africans, ASW as African American, and CHB and JPT as East Asian groups.…”