A HUMAN POPULATION STUDY OF THE GENETIC CONTROL OF X-INACTIVATION

摘要: ["Many X-linked disorders have been reported to manifest some degree in females. This is due preferential inactivation of the X-chromosome carrying normal allele and subsequent expression mutant majority cells. The determination which becomes inactivated believed be a random event, with each parental having an equal probability becoming inactivated. However, alleles identified inbred mouse strains that control X chromosome patterns resulting varying degrees skewed X-inactivation ratios. These alleles, termed controlling element (Xce) map center (XIC), only mice, effect ratios when they are heterozygous mouse. To determine if similar Xce exist humans, we markers (XIC) tested these variants observed I sequenced 30 kb XIC 15 unrelated X-chromosomes, identifying 18 single nucleotide changes, 5 insertion/deletion changes. Interestingly, 11 23 variant sites were found on two independent chromosomes distinct haplotype extends more than 50 within XIC. Further phylogenetic analysis has revealed all present chimpanzee samples revealing ancient ancestral haplotype. All but one SNPs strong disequilibrium across XIC.Eleven polymorphisms (SNPs), calculated frequencies between 5% -45%, genotyped 560 newborn any identify choice applied model. model compares genotypes homozygous there affect distribution. Each significant difference XCI distribution variances (pamp;lt; 0.05) sample exhibiting greater skewing."]