Germline mutations in the factor IX gene: a comparison of the pattern in Caucasians and non-Caucasians

Abstract

DNA samples of patients from around the world have been sequenced to precisely define the mutations in the factor IX gene resulting in hemophilia B. This study compares the patterns of independent mutation between 127 Caucasian and 44 non-Caucasian patients with hemophilia B. Caucasians and non-Caucasians are found to have similar patterns of transitions and transversions (both at CpG and at non-CpG sites) as well as insertions, deletions, microdeletions, and complex changes (chi 2 = 2.71, p = 0.922). An analysis of subgroups of transitions and transversions shows similar patterns among Caucasians and non-Caucasians (chi 2 = 2.98, p = 0.83). If the subset of non-Caucasian samples (24) in which the mutation is known to have occurred outside of the United States, Canada, and Europe (UCE) is compared to the Caucasian subset, the above conclusions are unchanged. The invariant nature of this pattern of mutation is most simply compatible with a predominance of endogenous processes or common mutagen exposure rather than mutagen exposure specifically associated with non-Caucasian status or non-Western lifestyle.

Novel pattern of P53 mutation in breast cancers from Austrian women.

“…The (25) and less than 10% of all mutations in the factor IX gene (26). The pattern of mutation in the factor IX gene is similar across multiple ethnically and geographically diverse populations and is believed to reflect the endogenous (background) pattern of mutation in man (27). Thus, the threefold excess of A:T-+T:A transversions in the Austrian group raises the possibility that there might be a factor contributing to mutagenesis that is more prevalent in that population.…”

Polyglutamine Expansion Reduces the Association of TATA-binding Protein with DNA and Induces DNA Binding-independent Neurotoxicity

“…A role for the TBP N terminus, and the polyQ domain in particular, in transcriptional activation at TATA-containing promoters has been suggested previously (10,11). In humans, the polyQ tract normally contains 25-42 glutamine residues (12). Expanded repeats of Ͼ42 glutamines generally result in SCA17 (13)(14)(15)(16), although reduced penetrance has been observed in the range of 43-49 glutamines (17).…”

Nine independentF9 mutations in the Mexican hemophilia B population: Nonrandom recurrences of point mutation events in the human germline

“…Multiple characteristics [reviewed in (Sommer, 1995;Sommer and Ketterling, 1996)], make human F9 a valuable model for studying recent germline mutations, inferring the endogenous pattern of mutation, and detecting the effects of environmental mutagens in the human germline. Previous analyses of F9 mutation types (e.g., transitions, transversions, insertions, deletions) found no significant difference between the mutation patterns of different populations (Gostout et al, 1993;Green et al, 1991;Bottema et al, 1990;Thorland et al, 1995), suggesting that endogenous processes account for most human germline mutations (Sommer, 1995). In addition, among an estimated 439 non-CpG bases within the coding region which cause hemophilia B no substitution hotspots have previously been identified.…”

“…Identification of polymorphic haplotypes confirmed the segregation patterns of alleles within the family pedigrees, the independence of identical mutations, and, for three, the germline origin. The MseI, BamHI, HinfI, XmnI, TaqI, 3´(RY)i, and HhaI polymorphisms within F9 were analyzed (Winship et al, 1993;Gostout et al, 1993;Jacobson et al, 1993;Sarkar et al, 1991).…”