&ring sing1e predisposing genetic risk factor for thrombosis cross and westminster ~~d i~~l school, ~~~~~~~~i~h , ~~~d~~ W6 ~R F , (25,26

No abstract

beta-globin gene haplotypes were determined for 196 normal (beta-A) and 419 thalassaemia (beta-Th) chromosomes of individuals from four different regions of the Indian subcontinent; North-west Pakistan, Gujarat, Punjab and Sindh. Analysis of beta-A and beta-Th haplotypes and haplotype-mutation associations in each regional group along with a consideration of Indian history provided information about the origin and spread of beta-thalassaemia mutations on the Indian subcontinent. The data are consistent with relatively recent and local origins for most beta-thalassaemia mutations. The frequencies of particular alleles differ markedly in various regions and these may be useful population markers. Of the high frequency alleles, intervening sequence 1 (IVS-1) nucleotide 5 (G-C) and codons 41/42 (-CTTT) appear to be older as suggested by multiple haplotype associations and a widespread geographical distribution. The microepidemiology of beta-thalassaemia in this region reflects considerable ethnic diversity, gene flow from population migration and natural selection by malaria infection.

Our results support the hypothesis that some BDNF gene polymorphisms may be contributing factors in the pathogenesis of BD. Our study also adds to the body of evidence associating the functional Val66Met polymorphism of BDNF with BD.

The a1 thalassaemia alleles in 501p thalassaemia heterozygotes originating from many parts of the United Arab Emirates (UAE) have been characterised using the allele specific priming technique of the polymerase chain reaction (PCR). The IVSI-5 (G-.C) mutation was found to be present in 66%, while six other alleles occurred at the much lower frequencies of 2% to 8%. These were codon 8/9 (+ G), IVSI-1, 3' end (-25 bp), codon 5 (-CT), IVSII-1 (G-)A), codon 30 (G-+C), and codon 15 (G-A). The mutation types and percentages are compared with other Mediterranean Arab countries and neighbouring areas. It is proposed that IVSI-5 and other Asian Indian mutations were introduced into the UAE by population migration from the region previously known as Baluchistan. These findings should be useful for genetic counselling and the development of a first trimester prenatal diagnosis programme based on direct detection of mutations in the UAE.