摘要:

SUMMARYWe have identified the molecular basis of the GAA*4 allozyme as a G to A transition at nt2065 which predicts the substitution of glutamic acid by lysine at codon 689 (E689K). The conclusion that this change represents the molecular basis of the GAA*4 allozyme is based on 1) presence of the G2065A in homozygosity in a known GAA*4 homozygote, 2) transient expression studies showing normal enzyme activity expressed by cDNA containing the G2065A transition and 3) isoelectric focusing studies showing a more cathodal pattern for the expressed product as compared to the common GAA*1, analogous to the patterns seen in normal and known GAA*4 lymphoid cells.

ISSN:0003-4800    

DOI:10.1111/j.1469-1809.1996.tb00433.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARYTheMinmouse is a model for human familial adenomatous polyposis (FAP), an autosomal dominant disease characterised by multiple adenomatous gastrointestinal polyps. The severity of theMinphenotype is modified by a locus (Mom1) on mouse chromosome 4, at a position syntenic with human chromosome 1p35‐p36. The secretory phospholipase A2 (Pla2s) gene is a candidate for this modifier locus and there is evidence that a locus on human chromosome 1p35‐p36 acts to modify the severity of human duodenal FAP. We have analysed the human secretory phospholipase A2 locus (PLA2G2A) for variants that could directly influence the FAP phenotype. We found noPLA2G2Avariants predicted to result in functional variation in the phospholipase A2 protein. TwoPLA2G2Apolymorphisms were, however, discovered, one a ‘silent’ base change in exon 3 and another in a non‐coding region. Three other variants (possible mutations) were found in non‐coding regions. In 70 FAP patients from 20 families, no associations were found between the severity of duodenal polyposis and anyPLA2G2Avariant. One allele at the exon 3 polymorphic site did, however, occur more often then expected in patients with relatively severe colonie FAP. Although of borderline statistical significance, this association, if genuine, is likely to result from linkage disequilibrium between thePLA2G2Aalleles studied and undetected genetic variation at a closely linked locus. The frequency of the alleles at both polymorphic sites has also been determined in the germ line of patients with sporadic colorectal adenomas and carcinomas and in random controls, but no differences were found among these groups. Our results suggest thatPLA2G2Avariants do not influence inherited or sporadic colonie tumours. A linked locus may be a modifier of human FAP, but does not influence the risk of colorectal tumours in the general

ISSN:0003-4800    

DOI:10.1111/j.1469-1809.1996.tb00434.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

ABSTRACTPeutz‐Jeghers' syndrome (PJS) is a disease with autosomal dominant inheritance, which is characterised by gastrointestinal hamartomata and characteristic melanin pigmentation. Three candidate sites for a PJS locus have recently been proposed, chromosomes 1p31‐p32, 6q25 and 6p11‐cen. At the first of these sites, a multipoint LOD score of 4.00 had been found, strongly suggesting genetic linkage to PJS. The last two candidate sites were suggested by the chromosomal breakpoints of a patient with an inv(6) and PJS. We have analysed up to 34 families in order to test each of the three candidate sites for linkage to PJS. No evidence was found in support of a Peutz‐Jeghers' syndrome locus on chromosome 1p31‐p32. The candidate region on 6q25 was also excluded. The region close to the centromere of chromosome 6 has not been excluded and there is some evidence of linkage to a marker near 6cen, although genetic heterogeneity in PJS must be proposed to account for a gene at

ISSN:0003-4800    

DOI:10.1111/j.1469-1809.1996.tb00435.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARYThe abundant and almost exclusive expression of OCP‐II protein in the mammalian cochlea has fuelled speculation that mutations in theOCP2gene may result in inherited forms of hearing impairment. We have identified several human sequences related toOCP2and sublocalised three of theseOCP2related loci to 4q12‐p14 or 4p16.2‐pter, 5q15‐q21.3 and 7p22‐q22 by PCR. 2 YACs with sequence consistent with the chromosome 7 locus were also used for FISH analysis and hybridised to chromosome 7q11. Our data suggest that the cytogenetic localisations of theseOCP2related sequences do not correlate with the precise chromosomal positions of deafness loci so far i

ISSN:0003-4800    

DOI:10.1111/j.1469-1809.1996.tb00436.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARYTo assess the relative contributions oftrans‐acting factors (replication and repair functions) andcis‐acting elements (repeat and flanking DNA composition) to the mechanism of trinucleotide repeat sequence mutation we have analysed the distribution of copy number polymorphisms at 12 loci associated with dynamic mutations in 15 populations of different ethnic origins. Genome wide instability of repeats in a particular population would be evidence oftrans‐acting factor instigation of the mutation process, whereas instability at a particular locus (perhaps even in several populations) would be evidence that the composition of the particular locus was the most significant factor contributing to mutation. TheFRA16Alocus is highly polymorphic in only the European population. Some other loci exhibit distinct distributions of alleles between different populations. Therefore sequences in the vicinity of the repeat ‐ theciscomponent of a particular locus ‐ appear(s) to be more important in the mutation mechanism than sporadic genome‐wide instability induced bytrans‐acting factors such as the DNA mismatch r

ISSN:0003-4800    

DOI:10.1111/j.1469-1809.1996.tb00437.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARYFive polymorphic markers on the Y‐chromosome (mostly microsatellites) were typed in 121 individuals from 13 populations around the world. With these markers 78 different haplotypes were detected. Haplotypes present more than once tend to be shared by individuals from the same population or continent. A reconstruction of haplotype phylogeny also indicates significant geographic structure in the data. Based on the similarity of the haplotypes, population relationships were examined and found to be largely concordant with those obtained with other markers. Even though the sample size and the number of markers are small, there is very signficant clustering of the haplotypes by continent of origi

ISSN:0003-4800    

DOI:10.1111/j.1469-1809.1996.tb00438.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARYMitochondrial DNA variation was studied in 100 Indians using the same set of six restriction enzymes used in the study of other world ethnic groups in order to compare and discern possible relationships of the Indian populations. Twenty nine mtDNA types were found including the ones from an earlier study (Semino et al. 1991) and unweighted pair‐group method (UPGMA) and maximum parsimony trees were constructed using the mtDNA types. The nucleotide diversity values were calculated using the maximum likelihood method. From a study of the shared mitochondrial DNA types and the parsimony tree (Fig. 2) we came to the conclusion that the Indian population is closer to Caucasians and has an admixture with Asians. The North Indian population appears to have a recent admixture of the Caucasian mtDNA types which is absent in the sout

ISSN:0003-4800    

DOI:10.1111/j.1469-1809.1996.tb00439.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARYAn analysis of genetic fitness was performed in Huntington's Disease (HD) and Spinocerebellar Ataxia 1 (SCA1) families. Two partially overlapping samples were used: clinically defined HD and SCA1 patients from families ascertained in definite geographical areas, and molecularly typed carriers of HD and SCA1 mutations (CAG trinucleotide expansions). In both cases, a control group of normal relatives was used. HD and SCA1 patients born before 1915–20 had more children than normal controls. Carriers of HD and SCA1 mutations, all in the low/medium expansion range (37–49 and 47–54 CAG repeats respectively), had a higher number of children than controls up to more recent times (1935–1950). The reproduction of heterozygotes for large expansions could be analysed only in subjects born after 1950 and provided indirect evidence of a lower than normal number of children. The above results fit a model based on a differential fitness according to the degree of expansion. Such a model predicts that 1) up to relatively recently the frequency of alleles in the low/medium range has been maintained or even increased by the increased fitness of their carriers, as well as by new mutations, and 2) the frequency of large expansions, part of which are lost at each generation, is maintained through further expansions of alleles in the low/medium expansion range. The implications of such a model on linkage disequilibrium and the possible spread of these diseases in future generations are di

ISSN:0003-4800    

DOI:10.1111/j.1469-1809.1996.tb00440.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

ISSN:0003-4800    

DOI:10.1111/j.1469-1809.1996.tb00441.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

ISSN:0003-4800    

DOI:10.1111/j.1469-1809.1996.tb00442.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY