Showing papers by "Wellcome Trust Centre for Human Genetics published in 1994"
TL;DR: Polygenic inheritance is indicated, with a major locus at the major histocompatibility complex of type 1 diabetes mellitus found in IDDM1 and IDDM2, and chromosome 18 may encode a fifth disease locus.
Abstract: We have searched the human genome for genes that predispose to type 1 (insulin-dependent) diabetes mellitus using semi-automated fluorescence-based technology and linkage analysis. In addition to IDDM1 (in the major histocompatibility complex on chromosome 6p21) and IDDM2 (in the insulin gene region on chromosome 11p15), eighteen different chromosome regions showed some positive evidence of linkage to disease. Linkages to chromosomes 11q (IDDM4) and 6q (IDDM5) were confirmed by replication, and chromosome 18 may encode a fifth disease locus. There are probably no genes with large effects aside from IDDM1. Therefore polygenic inheritance is indicated, with a major locus at the major histocompatibility complex.
1,326 citations
TL;DR: Evidence is reported for the localization of a previously undetected suscept-ibility locus for IDDM in the region of the FGF3 gene on chromo-some llq, showing the potential of genome-wide linkage studies to detect susceptibility loci in IDDM and other multifactor-ial disorders.
Abstract: LOCI in the major histocompatibility complex (MHC) on chromo-some 6 and the insulin (INS) region on chromosome 11 have been implicated in susceptibility to insulin-dependent diabetes mellitus (IDDM) through candidate gene investigations1–5, but they may account for less than 50% of genetic risk for the disease6. Genome-wide linkage studies have led to localization of more than 10 sus-ceptibility loci for insulin-dependent diabetes in the non-obese dia-betic (NOD) mouse7 and the BB rat8. Similar studies are now possible in humans through the development of dense genetic maps of highly informative microsatellite loci obtained using polymerase chain reaction analysis9. We have applied microsatellite markers from recent Genethon maps10,11, and other highly informative mar-kers, in a genome-wide linkage study in IDDM. Here we report evidence for the localization of a previously undetected suscept-ibility locus for IDDM in the region of the FGF3 gene on chromo-some llq. Our result shows the potential of genome-wide linkage studies to detect susceptibility loci in IDDM and other multifactor-ial disorders.
410 citations
TL;DR: To facilitate large–scale genetic mapping of the human genome, chromosome–specific sets of microsatellite marker loci suitable for use with a fluorescence–based automated DNA fragment analyser are developed.
Abstract: To facilitate large-scale genetic mapping of the human genome, we have developed chromosome-specific sets of microsatellite marker loci suitable for use with a fluorescence-based automated DNA fragment analyser. We present 254 dinucleotide repeat marker loci (80% from the Genethon genetic linkage map) arranged into 39 sets, covering all 22 autosomes and the X chromosome. The average distance between adjacent markers is 13 centiMorgans, and less than 4% of the genome lies more than 20 cM from the nearest marker. Each set of microsatellites consists of up to nine marker loci, with allele size ranges that do not overlap. We selected marker loci on the basis of their reliability in the polymerase chain reaction, polymorphism content, map position and the accuracy with which alleles can be scored automatically by the Genotyper(TM) program.
332 citations
TL;DR: This work presents a high resolution radiation hybrid map of human chromosome 11 using 506 sequence tagged sites (STSs) scored on a panel of 86 radiation hybrids, and finds that more than half of the STSs are polymorphic microsatellite loci.
Abstract: We present a high resolution radiation hybrid map of human chromosome 11 using 506 sequence tagged sites (STSs) scored on a panel of 86 radiation hybrids. The 506 STSs fall into 299 unique positions (average resolution of about 480 kilobases (kb)) that span the whole chromosome. A subset of 260 STSs (143 positions) form a framework map that has a resolution of approximately 1 megabase between adjacent positions and is ordered with odds of at least 1,000:1. The centromere was clearly defined with pericentric markers unambiguously assigned to the short or long arm. The map contains most genes (125) and expressed sequence tags (26) currently assigned to chromosome 11 and more than half of the STSs are polymorphic microsatellite loci. These markers and the map can be used for high resolution physical and genetic mapping.
154 citations