Bardet-Biedl syndrome in Newfoundland : molecular genetics of a rare recessive disorder in a small isolated population
Thesis (Ph.D.)--Memorial University of Newfoundland, 2001. Medicine Bibliography: leaves 197-218 Bardet-Biedl syndrome (BBS) is characterized by retinal dystrophy, dysmorphicextremities, renal structural abnormalities, obesity, and hypogenitalism in males. This autosomal recessive disorder is geneti...
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ftmemorialunivdc:oai:collections.mun.ca:theses3/85296 2023-05-15T17:23:32+02:00 Bardet-Biedl syndrome in Newfoundland : molecular genetics of a rare recessive disorder in a small isolated population Woods, Michael O., 1972- Memorial University of Newfoundland. Faculty of Medicine Canada--Newfoundland and Labrador 2001 1 v. (various foliations) : ill. (some col.), maps Image/jpeg; Application/pdf http://collections.mun.ca/cdm/ref/collection/theses3/id/85296 eng eng Electronic Theses and Dissertations (31.25 MB) -- http://collections.mun.ca/PDFs/theses/Woods_MichaelO.pdf a1541825 http://collections.mun.ca/cdm/ref/collection/theses3/id/85296 The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. Paper copy kept in the Centre for Newfoundland Studies, Memorial University Libraries Laurence-Moon-Biedl syndrome--Newfoundland and Labrador--Genetic aspects Bardet-Biedl Syndrome--genetics--Newfoundland and Labrador Text Electronic thesis or dissertation 2001 ftmemorialunivdc 2015-08-06T19:18:45Z Thesis (Ph.D.)--Memorial University of Newfoundland, 2001. Medicine Bibliography: leaves 197-218 Bardet-Biedl syndrome (BBS) is characterized by retinal dystrophy, dysmorphicextremities, renal structural abnormalities, obesity, and hypogenitalism in males. This autosomal recessive disorder is genetically heterogenous with four identified loci, BBS1-4 (1 lq, I6q, 3p and 15q respectively). BBS is a relatively rare disorder, but it is approximately ten times more prevalent in Newfoundland than in northern European populations. -- To investigate the high incidence of BBS in the Newfoundland population, members of 17 BBS families were analyzed by haplotype and linkage analyses. Initially, linkage of five families to BBSL one each to BBS2 and BBS3 and exclusion of six families from the four known BBS loci was observed. -- A large consanguineous Newfoundland BBS family, excluded from the four known BBS loci, was used to identify a fifth BBS gene locus (BBS5) on 2q31 in a genome-wide scan. However, this gene did not segregate in any other of the five unlinked families. Therefore, another genome scan was implemented on a consanguineous family excluded from the five BBS loci. Evidence of a sixth BBS gene (BBS6) on 20pl2 was established and the critical interval narrowed to 2 cM using five other unlinked families. Located within this region is a putative chaperonin gene (MKKS) involved in McKusick-Kaufman syndrome, a disorder with an overlapping phenotype with BBS. When MKKS was screened for mutations in six Newfoundland BBS families, one missense and two frameshift mutations were identified. Thus, MKKS was the first gene identified to cause BBS. Remarkably, one family could be excluded from all six BBS loci, indicating the existence of a seventh BBS gene (BBS7). -- By mutational and/or haplotype and linkage analyses, it was possible to assign 14 of the 17 Newfoundland BBS families to known BBS loci. Six families had mutations in MKKS/BBS6, five families were associated with the BBS1 locus, and one family to each of the BBS2, BBS3 and BBSS loci. Additionally, one family was excluded from the six known BBS loci. The discovery of MKKS/BBS6 should aid in the ascertainment of other BBS genes and contribute to the basic understanding of the manifestations of BBS. Thesis Newfoundland studies University of Newfoundland Memorial University of Newfoundland: Digital Archives Initiative (DAI) Canada Newfoundland |
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Memorial University of Newfoundland: Digital Archives Initiative (DAI) |
op_collection_id |
ftmemorialunivdc |
language |
English |
topic |
Laurence-Moon-Biedl syndrome--Newfoundland and Labrador--Genetic aspects Bardet-Biedl Syndrome--genetics--Newfoundland and Labrador |
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Laurence-Moon-Biedl syndrome--Newfoundland and Labrador--Genetic aspects Bardet-Biedl Syndrome--genetics--Newfoundland and Labrador Woods, Michael O., 1972- Bardet-Biedl syndrome in Newfoundland : molecular genetics of a rare recessive disorder in a small isolated population |
topic_facet |
Laurence-Moon-Biedl syndrome--Newfoundland and Labrador--Genetic aspects Bardet-Biedl Syndrome--genetics--Newfoundland and Labrador |
description |
Thesis (Ph.D.)--Memorial University of Newfoundland, 2001. Medicine Bibliography: leaves 197-218 Bardet-Biedl syndrome (BBS) is characterized by retinal dystrophy, dysmorphicextremities, renal structural abnormalities, obesity, and hypogenitalism in males. This autosomal recessive disorder is genetically heterogenous with four identified loci, BBS1-4 (1 lq, I6q, 3p and 15q respectively). BBS is a relatively rare disorder, but it is approximately ten times more prevalent in Newfoundland than in northern European populations. -- To investigate the high incidence of BBS in the Newfoundland population, members of 17 BBS families were analyzed by haplotype and linkage analyses. Initially, linkage of five families to BBSL one each to BBS2 and BBS3 and exclusion of six families from the four known BBS loci was observed. -- A large consanguineous Newfoundland BBS family, excluded from the four known BBS loci, was used to identify a fifth BBS gene locus (BBS5) on 2q31 in a genome-wide scan. However, this gene did not segregate in any other of the five unlinked families. Therefore, another genome scan was implemented on a consanguineous family excluded from the five BBS loci. Evidence of a sixth BBS gene (BBS6) on 20pl2 was established and the critical interval narrowed to 2 cM using five other unlinked families. Located within this region is a putative chaperonin gene (MKKS) involved in McKusick-Kaufman syndrome, a disorder with an overlapping phenotype with BBS. When MKKS was screened for mutations in six Newfoundland BBS families, one missense and two frameshift mutations were identified. Thus, MKKS was the first gene identified to cause BBS. Remarkably, one family could be excluded from all six BBS loci, indicating the existence of a seventh BBS gene (BBS7). -- By mutational and/or haplotype and linkage analyses, it was possible to assign 14 of the 17 Newfoundland BBS families to known BBS loci. Six families had mutations in MKKS/BBS6, five families were associated with the BBS1 locus, and one family to each of the BBS2, BBS3 and BBSS loci. Additionally, one family was excluded from the six known BBS loci. The discovery of MKKS/BBS6 should aid in the ascertainment of other BBS genes and contribute to the basic understanding of the manifestations of BBS. |
author2 |
Memorial University of Newfoundland. Faculty of Medicine |
format |
Thesis |
author |
Woods, Michael O., 1972- |
author_facet |
Woods, Michael O., 1972- |
author_sort |
Woods, Michael O., 1972- |
title |
Bardet-Biedl syndrome in Newfoundland : molecular genetics of a rare recessive disorder in a small isolated population |
title_short |
Bardet-Biedl syndrome in Newfoundland : molecular genetics of a rare recessive disorder in a small isolated population |
title_full |
Bardet-Biedl syndrome in Newfoundland : molecular genetics of a rare recessive disorder in a small isolated population |
title_fullStr |
Bardet-Biedl syndrome in Newfoundland : molecular genetics of a rare recessive disorder in a small isolated population |
title_full_unstemmed |
Bardet-Biedl syndrome in Newfoundland : molecular genetics of a rare recessive disorder in a small isolated population |
title_sort |
bardet-biedl syndrome in newfoundland : molecular genetics of a rare recessive disorder in a small isolated population |
publishDate |
2001 |
url |
http://collections.mun.ca/cdm/ref/collection/theses3/id/85296 |
op_coverage |
Canada--Newfoundland and Labrador |
geographic |
Canada Newfoundland |
geographic_facet |
Canada Newfoundland |
genre |
Newfoundland studies University of Newfoundland |
genre_facet |
Newfoundland studies University of Newfoundland |
op_source |
Paper copy kept in the Centre for Newfoundland Studies, Memorial University Libraries |
op_relation |
Electronic Theses and Dissertations (31.25 MB) -- http://collections.mun.ca/PDFs/theses/Woods_MichaelO.pdf a1541825 http://collections.mun.ca/cdm/ref/collection/theses3/id/85296 |
op_rights |
The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. |
_version_ |
1766113111263150080 |