Linkage disequilibrium mapping in the Newfoundland population: a re-evaluation of the refinement of the Bardet-Biedl syndrome 1 critical interval
Genetically isolated populations, such as Newfoundland, have contributed greatly to the identification of disease-causing genes. A linkage disequilibrium (LD) study involving six Newfoundland families predicted a critical interval for Bardet- Biedl syndrome 1 (BBS1) (Young et al. in Am J Hum Genet 6...
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ftucl:oai:eprints.ucl.ac.uk.OAI2:39582 2023-05-15T17:16:58+02:00 Linkage disequilibrium mapping in the Newfoundland population: a re-evaluation of the refinement of the Bardet-Biedl syndrome 1 critical interval Fan, YL Green, JS Ross, AJ Beales, PL Parfrey, PS Davidson, WS 2005 http://discovery.ucl.ac.uk/39582/ unknown Human Genetics , 116 (1-2) 62 - 71. (2005) 1 1999 A alleles Analysis AND Bardet-Biedl Syndrome BARDET-BIEDL-SYNDROME BOTH CHROMOSOME CHROMOSOMES DISEASE DISORDER DISORDERS families FAMILY FOR Founder Effect FREQUENCIES FREQUENCY GENE Genes Genetic GENETIC-VARIATION Haplotypes hereditary IDENTIFICATION INDIVIDUALS IS JOURNAL LINKAGE LINKAGE DISEQUILIBRIUM mapping MUTATION MUTATIONS NO NO EVIDENCE OF PATIENT patients Population prediction REGION SINGLE SUBSEQUENT Syndrome THE Article 2005 ftucl 2014-08-07T23:05:12Z Genetically isolated populations, such as Newfoundland, have contributed greatly to the identification of disease-causing genes. A linkage disequilibrium (LD) study involving six Newfoundland families predicted a critical interval for Bardet- Biedl syndrome 1 (BBS1) (Young et al. in Am J Hum Genet 65:1680-1687, 1999), but the subsequent identification of BBS1 revealed that it lies outside this region. This suggested that either there is another gene responsible for BBS in these families or the Newfoundland population may not be ideal for LD studies. We screened these six Newfoundland families for mutations in BBS1 and found that affected individuals in five of them were homozygous for the same M390R mutation. There was no evidence for any BBS1 mutation it! the affected individual in the sixth family. Therefore, one of the criteria for LD mapping was not met; namely, there should be a single disease- causing allele in the population. Haplotype analysis of unaffected individuals from south-west Newfoundland and English BBS1 patients homozygous for M390R, revealed that a second criterion for LD mapping was violated. The M390R mutation occurred in a common haplotype and both of these chromosomes, the ancestral wild-type and disease-causing haplotypes, were introduced to Newfoundland and spread by a founder effect. Moreover, it was found that disease-associated alleles occurred at relatively high frequencies in normal haplotypes and this probably accounted for the incorrect prediction in the previous LD study. Knowing the amount of genetic variation and its distribution in the Newfoundland population would be useful to maximize its potential for mapping hereditary disorders Article in Journal/Newspaper Newfoundland University College London: UCL Discovery |
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University College London: UCL Discovery |
op_collection_id |
ftucl |
language |
unknown |
topic |
1 1999 A alleles Analysis AND Bardet-Biedl Syndrome BARDET-BIEDL-SYNDROME BOTH CHROMOSOME CHROMOSOMES DISEASE DISORDER DISORDERS families FAMILY FOR Founder Effect FREQUENCIES FREQUENCY GENE Genes Genetic GENETIC-VARIATION Haplotypes hereditary IDENTIFICATION INDIVIDUALS IS JOURNAL LINKAGE LINKAGE DISEQUILIBRIUM mapping MUTATION MUTATIONS NO NO EVIDENCE OF PATIENT patients Population prediction REGION SINGLE SUBSEQUENT Syndrome THE |
spellingShingle |
1 1999 A alleles Analysis AND Bardet-Biedl Syndrome BARDET-BIEDL-SYNDROME BOTH CHROMOSOME CHROMOSOMES DISEASE DISORDER DISORDERS families FAMILY FOR Founder Effect FREQUENCIES FREQUENCY GENE Genes Genetic GENETIC-VARIATION Haplotypes hereditary IDENTIFICATION INDIVIDUALS IS JOURNAL LINKAGE LINKAGE DISEQUILIBRIUM mapping MUTATION MUTATIONS NO NO EVIDENCE OF PATIENT patients Population prediction REGION SINGLE SUBSEQUENT Syndrome THE Fan, YL Green, JS Ross, AJ Beales, PL Parfrey, PS Davidson, WS Linkage disequilibrium mapping in the Newfoundland population: a re-evaluation of the refinement of the Bardet-Biedl syndrome 1 critical interval |
topic_facet |
1 1999 A alleles Analysis AND Bardet-Biedl Syndrome BARDET-BIEDL-SYNDROME BOTH CHROMOSOME CHROMOSOMES DISEASE DISORDER DISORDERS families FAMILY FOR Founder Effect FREQUENCIES FREQUENCY GENE Genes Genetic GENETIC-VARIATION Haplotypes hereditary IDENTIFICATION INDIVIDUALS IS JOURNAL LINKAGE LINKAGE DISEQUILIBRIUM mapping MUTATION MUTATIONS NO NO EVIDENCE OF PATIENT patients Population prediction REGION SINGLE SUBSEQUENT Syndrome THE |
description |
Genetically isolated populations, such as Newfoundland, have contributed greatly to the identification of disease-causing genes. A linkage disequilibrium (LD) study involving six Newfoundland families predicted a critical interval for Bardet- Biedl syndrome 1 (BBS1) (Young et al. in Am J Hum Genet 65:1680-1687, 1999), but the subsequent identification of BBS1 revealed that it lies outside this region. This suggested that either there is another gene responsible for BBS in these families or the Newfoundland population may not be ideal for LD studies. We screened these six Newfoundland families for mutations in BBS1 and found that affected individuals in five of them were homozygous for the same M390R mutation. There was no evidence for any BBS1 mutation it! the affected individual in the sixth family. Therefore, one of the criteria for LD mapping was not met; namely, there should be a single disease- causing allele in the population. Haplotype analysis of unaffected individuals from south-west Newfoundland and English BBS1 patients homozygous for M390R, revealed that a second criterion for LD mapping was violated. The M390R mutation occurred in a common haplotype and both of these chromosomes, the ancestral wild-type and disease-causing haplotypes, were introduced to Newfoundland and spread by a founder effect. Moreover, it was found that disease-associated alleles occurred at relatively high frequencies in normal haplotypes and this probably accounted for the incorrect prediction in the previous LD study. Knowing the amount of genetic variation and its distribution in the Newfoundland population would be useful to maximize its potential for mapping hereditary disorders |
format |
Article in Journal/Newspaper |
author |
Fan, YL Green, JS Ross, AJ Beales, PL Parfrey, PS Davidson, WS |
author_facet |
Fan, YL Green, JS Ross, AJ Beales, PL Parfrey, PS Davidson, WS |
author_sort |
Fan, YL |
title |
Linkage disequilibrium mapping in the Newfoundland population: a re-evaluation of the refinement of the Bardet-Biedl syndrome 1 critical interval |
title_short |
Linkage disequilibrium mapping in the Newfoundland population: a re-evaluation of the refinement of the Bardet-Biedl syndrome 1 critical interval |
title_full |
Linkage disequilibrium mapping in the Newfoundland population: a re-evaluation of the refinement of the Bardet-Biedl syndrome 1 critical interval |
title_fullStr |
Linkage disequilibrium mapping in the Newfoundland population: a re-evaluation of the refinement of the Bardet-Biedl syndrome 1 critical interval |
title_full_unstemmed |
Linkage disequilibrium mapping in the Newfoundland population: a re-evaluation of the refinement of the Bardet-Biedl syndrome 1 critical interval |
title_sort |
linkage disequilibrium mapping in the newfoundland population: a re-evaluation of the refinement of the bardet-biedl syndrome 1 critical interval |
publishDate |
2005 |
url |
http://discovery.ucl.ac.uk/39582/ |
genre |
Newfoundland |
genre_facet |
Newfoundland |
op_source |
Human Genetics , 116 (1-2) 62 - 71. (2005) |
_version_ |
1766082681541492736 |