Haplotype block structure study of the CFTR gene. Most variants are associated with the M470 allele in several European populations

An average of about 1700 CFTR (cystic fibrosis transmembrane conductance regulator) alleles from normal individuals from different European populations were extensively screened for DNA sequence variation. A total of 80 variants were observed: 61 coding SNSs (results already published), 13 noncoding SNSs, three STRs, two short deletions, and one nucleotide insertion. Eight DNA variants were classified as non-CF causing due to their high frequency of occurrence. Through this survey the CFTR has become the most exhaustively studied gene for its coding sequence variability and, though to a lesser extent, for its noncoding sequence variability as well. Interestingly, most variation was associated with the M470 allele, while the V470 allele showed an 'extended haplotype homozygosity' (EHH). These findings make us suggest a role for selection acting either on the M470V itself or through an hitchhiking mechanism involving a second site. The possible ancient origin of the V allele in an 'out of Africa' time frame is discussed

Two Ethnic-Specific Polymorphisms in the Human Beta Pseudogene of Hemoglobin

Two polymorphic sites, — 107 C -\u3e T and — 100 G -\u3e C with respect to the cap site of the human beta pseudogene of the hemoglobin gene, are described. They have been studied in five European, one Indian, two Asian, and two sub-Saharan African populations. The — 107 C -\u3e• T site turned out to be polymorphic in all five European populations and the Indian population (pooled q = 0.142 ± 0.018) and in the two Asian populations (pooled q = 0.073 ± 0.025), but it was monomorphic in the two sub-Saharan populations. On the contrary, the — 100 G -\u3e C site was polymorphic in the two sub-Saharan samples (q = 0.093 ± 0.024), but the variant allele was not found in any of the European, Indian, or Asian samples. Thus this only 8-bp-long stretch of DNA is informative for estimating the extent of genetic admixture in sub-Saharan Africans

Confirmation of the Potential Usefulness of Two Human Beta Globin Pseudogene Markers to Estimate Gene Flows to and from Sub-Saharan Africans

Two polymorphic sites, –107 and –100 with respect to the “cap” site of the human beta globin pseudogene, recently discovered in our laboratory, turned out to have an ethnically complementary distribution. The first site is polymorphic in Europeans, North Africans, Indians (Hindu), and Oriental Asians, and monomorphic in sub-Saharan Africans. Conversely, the second site is polymorphic in sub-Saharan African populations and monomorphic in the aforementioned populations. Here we report the gene frequencies of these two polymorphic sites in nine additional populations (Egyptians, Spaniards, Japanese, Chinese, Filipinos, Vietnamese, Africans from Togo and from Benin, and Pygmies), confirming their ethnospecificity and, through the analysis of these two markers in Oromo and Amhara of Ethiopia (two mixed populations), their usefulness in genetic admixture studies. Moreover, we studied another marker polymorphic in sub-Saharan African populations only, a TaqI restriction fragment length polymorphism located in the same region as the present markers, demonstrating the absence of linkage disequilibrium between it and the –100 site, so that we can exclude that the information they provide is redundant