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Age and origin of two common MLH1 mutations predisposing to hereditary colon cancer.

https://arctichealth.org/en/permalink/ahliterature210534
Source
Am J Hum Genet. 1996 Dec;59(6):1243-51
Publication Type
Article
Date
Dec-1996
Author
A L Moisio
P. Sistonen
J. Weissenbach
A. de la Chapelle
P. Peltomäki
Author Affiliation
Department of Medical Genetics, Haartman Institute, University of Helsinki, Finland.
Source
Am J Hum Genet. 1996 Dec;59(6):1243-51
Date
Dec-1996
Language
English
Publication Type
Article
Keywords
Adult
Age Factors
Age of Onset
Chromosome Mapping - methods
Colorectal Neoplasms, Hereditary Nonpolyposis - genetics
DNA Repair - genetics
DNA, Satellite - genetics
Finland
Genetic markers
Genetics, Population
Haplotypes - genetics
Humans
Linkage Disequilibrium
Middle Aged
Pedigree
Abstract
Two mutations in the DNA mismatch repair gene MLH1, referred to as mutations 1 and 2, are frequent among Finnish kindreds with hereditary nonpolyposis colorectal cancer (HNPCC). In order to assess the ages and origins of these mutations, we constructed a map of 15 microsatellite markers around MLH1 and used this information in haplotype analyses of 19 kindreds with mutation 1 and 6 kindreds with mutation 2. All kindreds with mutation 1 showed a single allele for the intragenic marker D3S1611 that was not observed on any unaffected chromosome. They also shared portions of a haplotype of 4-15 markers encompassing 2.0-19.0 cM around MLH1. All kindreds with mutation 2 shared another allele for D3S1611 and a conserved haplotype of 5-14 markers spanning 2.0-15.0 cM around MLH1. The degree of haplotype conservation was used to estimate the ages of these two mutations. While some recessive disease genes have been estimated to have existed and spread for as long as thousands of generations worldwide and hundreds of generations in the Finnish population, our analyses suggest that the spread of mutation 1 started 16-43 generations (400-1,075 years) ago and that of mutation 2 some 5-21 generations (125-525 years) ago. These datings are compatible with our genealogical results identifying a common ancestor born in the 16th and 18th century, respectively. Overall, our results indicate that all Finnish kindreds studied to date showing either mutation 1 or mutation 2 are due to single ancestral founding mutations relatively recent in origin in the population. Alternatively, the mutations arose elsewhere earlier and were introduced in Finland more recently.
Notes
Cites: Hereditas. 1972;71(2):195-2364680662
Cites: Genome Res. 1995 Aug;5(1):42-528717054
Cites: Science. 1989 Sep 8;245(4922):1073-802570460
Cites: Hum Mol Genet. 1996 Jun;5(6):763-98776590
Cites: Annu Rev Genet. 1995;29:329-488825478
Cites: Science. 1990 Oct 12;250(4978):245-502218528
Cites: Dis Colon Rectum. 1991 May;34(5):424-52022152
Cites: Am J Hum Genet. 1991 Dec;49(6):1174-881746551
Cites: Am J Hum Genet. 1992 Mar;50(3):619-281347197
Cites: Science. 1993 May 7;260(5109):810-28484120
Cites: Genomics. 1993 Jun;16(3):720-58325646
Cites: Hum Mol Genet. 1993 Aug;2(8):1229-348104628
Cites: J Med Genet. 1993 Oct;30(10):857-658230163
Cites: Cell. 1993 Dec 17;75(6):1215-258261515
Cites: Nature. 1994 Mar 17;368(6468):258-618145827
Cites: Cancer Detect Prev. 1994;18(1):57-638162607
Cites: Nat Genet. 1992 Nov;2(3):204-111345170
Cites: Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):6054-88016114
Cites: Nature. 1994 Sep 1;371(6492):75-808072530
Cites: Nat Genet. 1994 Jun;7(2):169-757920636
Cites: Lancet. 1995 Mar 18;345(8951):7277885145
Cites: Nat Genet. 1995 Feb;9(2):152-97719342
Cites: Nat Genet. 1995 Feb;9(2):99-1017719352
Cites: Dis Colon Rectum. 1995 Jun;38(6):588-937774468
Cites: Am J Hum Genet. 1995 Jul;57(1):95-1027611301
Cites: Nat Med. 1995 Nov;1(11):1203-67584997
Cites: Int J Cancer. 1995 Dec 20;64(6):430-38550246
Cites: Am J Hum Genet. 1996 Feb;58(2):271-808571953
Cites: Nature. 1996 Mar 14;380(6570):152-48600387
Cites: Am J Hum Genet. 1996 Mar;58(3):506-128644710
Cites: Proc Natl Acad Sci U S A. 1987 May;84(9):2882-53033668
PubMed ID
8940269 View in PubMed
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Close linkage to chromosome 3p and conservation of ancestral founding haplotype in hereditary nonpolyposis colorectal cancer families.

https://arctichealth.org/en/permalink/ahliterature217953
Source
Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):6054-8
Publication Type
Article
Date
Jun-21-1994
Author
M. Nyström-Lahti
P. Sistonen
J P Mecklin
L. Pylkkänen
L A Aaltonen
H. Järvinen
J. Weissenbach
A. de la Chapelle
P. Peltomäki
Author Affiliation
Department of Medical Genetics, University of Helsinki, Finland.
Source
Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):6054-8
Date
Jun-21-1994
Language
English
Publication Type
Article
Keywords
Adenoma - genetics
Alleles
Chromosome Mapping
Chromosomes, Human, Pair 3
Colorectal Neoplasms, Hereditary Nonpolyposis - genetics
DNA, Satellite - genetics
Female
Finland
Genetic Linkage
Genetic markers
Genotype
Haplotypes - genetics
Humans
Lod Score
Male
Pedigree
Registries
Software
Abstract
A susceptibility to hereditary nonpolyposis colorectal cancer (HNPCC) was recently shown to be due to mutations in the MSH2 gene on chromosome 2p. A second susceptibility locus has been mapped to chromosome 3p in two families. The present report describes the results of a genetic study of Finnish HNPCC kindreds. Of 18 apparently unrelated families living in different parts of the country, 11 could be genealogically traced to a common ancestry dating at least 13 generations back in a small geographic area. Linkage studies were possible in 9 families, revealing conclusive or probable linkage to markers on 3p in 8. Five of these were among those having shared ancestry. The location of the gene was refined by a linkage study comprising 12 marker loci. By analysis of recombinations in such families, the HNPCC locus could be assigned to the 1-centimorgan interval between marker loci D3S1561 and D3S1298. A haplotype encompassing 10 centimorgans around the HNPCC locus was conserved in five of the pedigrees with shared ancestry and present in 2 further families in which linkage analysis was not possible. Our results suggest the presence of a widespread single ancestral founding mutation. Moreover, the map position of the 3p gene for HNPCC susceptibility was greatly refined.
Notes
Cites: Hum Mol Genet. 1992 May;1(2):131-31301149
Cites: Hum Hered. 1992;42(6):337-461493912
Cites: Science. 1993 May 7;260(5109):810-28484120
Cites: Science. 1993 May 7;260(5109):812-68484121
Cites: Genomics. 1993 Jun;16(3):720-58325646
Cites: Cytogenet Cell Genet. 1994;65(1-2):2-508104766
Cites: J Med Genet. 1993 Oct;30(10):857-658230163
Cites: Cell. 1993 Dec 3;75(5):1027-388252616
Cites: Nat Genet. 1993 Nov;5(3):279-827903889
Cites: Science. 1994 Mar 18;263(5153):1625-98128251
Cites: Cancer Detect Prev. 1994;18(1):57-638162607
Cites: Proc Natl Acad Sci U S A. 1984 Jun;81(11):3443-66587361
Cites: Dis Colon Rectum. 1986 Mar;29(3):160-43943429
Cites: Dis Colon Rectum. 1991 May;34(5):424-52022152
Cites: Cancer Res. 1991 Aug 15;51(16):4135-401868434
Cites: Cancer. 1991 Sep 1;68(5):1109-121913482
Cites: Cancer Res. 1992 Aug 15;52(16):4530-31643645
Cites: Ann Hum Genet. 1992 May;56(Pt 2):99-1031503398
Cites: Nature. 1992 Oct 29;359(6398):794-8011436057
Cites: Gastroenterology. 1993 May;104(5):1535-498482467
PubMed ID
8016114 View in PubMed
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A common gene for juvenile and adult-onset primary open-angle glaucomas confined on chromosome 1q.

https://arctichealth.org/en/permalink/ahliterature215000
Source
Am J Hum Genet. 1995 Jun;56(6):1431-42
Publication Type
Article
Date
Jun-1995
Author
J. Morissette
G. Côté
J L Anctil
M. Plante
M. Amyot
E. Héon
G E Trope
J. Weissenbach
V. Raymond
Author Affiliation
Centre de Recherche, Université Laval, Québec, Canada.
Source
Am J Hum Genet. 1995 Jun;56(6):1431-42
Date
Jun-1995
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Aged
Base Sequence
Child
Child, Preschool
Chromosome Mapping
Chromosomes, Human, Pair 1 - genetics
DNA, Satellite
Female
Founder Effect
France - ethnology
Genetic markers
Glaucoma, Open-Angle - classification - epidemiology - genetics
Haplotypes
Humans
Longitudinal Studies
Male
Middle Aged
Molecular Sequence Data
Pedigree
Phenotype
Quebec - epidemiology
Recombination, Genetic
Abstract
Primary open-angle glaucoma (POAG), which causes progressive loss of the visual fields, was subdivided into two groups according to age at onset: (1) chronic open-angle glaucoma (COAG) diagnosed after age 40 years and (2) juvenile open-angle glaucoma (JOAG) diagnosed between 3 years of age and early adulthood. A JOAG gene (GLC1A) was recently mapped to chromosome 1q. We studied 142 members of a huge multigenerational French Canadian family affected with autosomal dominant POAG. Either JOAG or COAG was diagnosed in 40 patients. Six subjects were also diagnosed with ocular hypertension (OHT), which may lead to POAG. To localize a common disease gene that might be responsible for both glaucoma subsets, we performed linkage analysis considering JOAG and COAG under the same phenotypic category. JOAG/COAG was tightly linked to seven microsatellite markers on chromosome 1q23-q25; a maximum lod score of 6.62 was obtained with AF-M278ye5. To refine the disease locus, we exploited a recombination mapping strategy based on a unique founder effect. The same characteristic haplotype, composed of 14 markers spanning 12 cM between loci D1S196 and D1S212, was recognized in all persons affected by JOAG, COAG, or OHT, but it did not occur in unaffected spouses and in normal family members > 35 years of age, except for three obligatory carriers. Key recombination events confined the disease region within a 9-cM interval between loci D1S445 and D1S416/D1S480. These observations demonstrate that the GLC1A gene is responsible for both adult-onset and juvenile glaucomas and suggest that the JOAG and COAG categories within this family may be part of a clinical continuum artificially divided at age 40 years.
Notes
Cites: Nature. 1990 Jun 28;345(6278):823-51972783
Cites: Hum Genet. 1991 May;87(1):73-802037285
Cites: Am J Hum Genet. 1991 Jul;49(1):68-752063878
Cites: Nature. 1992 Oct 29;359(6398):794-8011436057
Cites: Ophthalmology. 1993 Apr;100(4):524-98479711
Cites: Nat Genet. 1992 Apr;1(1):3-61301996
Cites: Nat Genet. 1992 Jun;1(3):192-51303233
Cites: Nat Genet. 1993 May;4(1):47-508513321
Cites: Int Ophthalmol Clin. 1993 Spring;33(2):101-208325726
Cites: Nature. 1993 Dec 16;366(6456):698-7018259213
Cites: Am J Ophthalmol. 1966 Apr;61(4):652-655931261
Cites: Can J Ophthalmol. 1968 Oct;3(4):330-65727757
Cites: Arch Ophthalmol. 1970 Nov;84(5):579-825478882
Cites: Trans Ophthalmol Soc U K. 1976 Apr;96(1):28-321070856
Cites: Am J Epidemiol. 1983 Aug;118(2):166-916349332
Cites: Am J Hum Genet. 1984 Mar;36(2):460-56585139
Cites: In Vitro. 1984 Nov;20(11):856-86519667
Cites: Am J Hum Genet. 1985 May;37(3):482-983859205
Cites: Ann Ophthalmol. 1985 Dec;17(12):739-414091373
Cites: Lancet. 1987 Jul 18;2(8551):156-72885615
Cites: Nucleic Acids Res. 1987 Nov 25;15(22):96113684611
Cites: Science. 1988 Apr 8;240(4849):185-83353714
Cites: Neuron. 1989 Aug;3(2):183-902576211
Cites: Am J Hum Genet. 1994 Jan;54(1):62-708279471
Cites: Am J Hum Genet. 1994 Jan;54(1):79-878279473
Cites: Am J Hum Genet. 1994 Jan;54(1):88-948279474
Cites: Nat Genet. 1993 Dec;5(4):392-68298649
Cites: Nat Genet. 1994 Jan;6(1):47-518136834
Cites: Hum Mol Genet. 1994 Feb;3(2):351-48004108
Cites: Hum Mol Genet. 1994 Mar;3(3):459-638012358
Cites: Nat Genet. 1994 Apr;6(4):391-38054980
Cites: Genomics. 1994 May 15;21(2):299-3038088822
Cites: Nat Genet. 1994 Jun;7(2 Spec No):246-3397545953
Cites: Br J Ophthalmol. 1964 Mar;48:143-714193667
Cites: Am J Ophthalmol. 1965 Jul;60:91-514310076
Cites: Br J Ophthalmol. 1962 Sep;46(9):513-2218170808
Comment In: Am J Hum Genet. 1996 Jan;58(1):243-48554064
PubMed ID
7762566 View in PubMed
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Congenital nephrotic syndrome of the Finnish type maps to the long arm of chromosome 19.

https://arctichealth.org/en/permalink/ahliterature59399
Source
Am J Hum Genet. 1994 May;54(5):757-64
Publication Type
Article
Date
May-1994
Author
M. Kestilä
M. Männikkö
C. Holmberg
G. Gyapay
J. Weissenbach
E R Savolainen
L. Peltonen
K. Tryggvason
Author Affiliation
Biocenter, University of Oulu, Finland.
Source
Am J Hum Genet. 1994 May;54(5):757-64
Date
May-1994
Language
English
Publication Type
Article
Keywords
Cell Line
Cells, Cultured
Chromosome Mapping
Chromosomes, Human, Pair 19
DNA, Satellite - analysis
Female
Finland - epidemiology
Genes, Recessive
Humans
Incidence
Infant, Newborn
Linkage (Genetics)
Lymphocytes - metabolism
Male
Nephrotic Syndrome - congenital - epidemiology - genetics
Pedigree
Polymorphism, Genetic
Recombination, Genetic
Research Support, Non-U.S. Gov't
Skin - metabolism
Abstract
Congenital nephrotic syndrome of the Finnish type (CNF) is an autosomal recessive disease that is characterized by massive proteinuria and nephrotic syndrome at birth. CNF represents a unique, apparently specific dysfunction of the renal basement membranes, and the estimated incidence of CNF in the isolated population of Finland is 1 in 8,000 newborns. The basic defect is unknown, and no specific biochemical defect or chromosomal aberrations have been described. Here we report the assignment of the CNF locus to 19q12-q13.1 on the basis of linkage analyses in 17 Finnish families. Multipoint analyses and observed recombination events place the CNF locus between multiallelic markers D19S416 and D19S224, and the significant linkage disequilibrium observed suggests that the CNF gene lies in the immediate vicinity of the markers D19S224 and D19S220.
PubMed ID
8178817 View in PubMed
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Cornea plana congenita gene assigned to the long arm of chromosome 12 by linkage analysis.

https://arctichealth.org/en/permalink/ahliterature215558
Source
Genomics. 1995 Mar 20;26(2):290-3
Publication Type
Article
Date
Mar-20-1995
Author
E. Tahvanainen
H. Forsius
E. Karila
S. Ranta
M. Eerola
J. Weissenbach
P. Sistonen
A. de la Chapelle
Author Affiliation
Department of Medical Genetics, University of Helsinki, Finland.
Source
Genomics. 1995 Mar 20;26(2):290-3
Date
Mar-20-1995
Language
English
Publication Type
Article
Keywords
Adult
Child
Chromosome Mapping
Chromosomes, Human, Pair 12
Cornea - abnormalities - embryology
Corneal Dystrophies, Hereditary - epidemiology - genetics
Female
Finland - epidemiology
Genes, Recessive
Genetic markers
Humans
Lod Score
Male
Recombination, Genetic
Abstract
We report the mapping of the locus for autosomal recessive cornea plana congenita (CNA2; MIM 217300) by linkage analysis to the approximately 10-cM interval between markers D12S82 and D12S327. The recessively inherited disorder studied here is more severe than dominant forms. Its main manifestations are reduced curvature and hazy limbus of the cornea, opacities in the corneal stroma, and marked corneal arcus at early age. Our results provide a starting point for the positional cloning of CNA2 and the elucidation of the pathogenesis of the disease.
PubMed ID
7601455 View in PubMed
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Evidence of a non-MHC susceptibility locus in type I diabetes linked to HLA on chromosome 6.

https://arctichealth.org/en/permalink/ahliterature48229
Source
Am J Hum Genet. 1997 Jan;60(1):174-87
Publication Type
Article
Date
Jan-1997
Author
M. Delépine
F. Pociot
C. Habita
L. Hashimoto
P. Froguel
J. Rotter
A. Cambon-Thomsen
I. Deschamps
S. Djoulah
J. Weissenbach
J. Nerup
M. Lathrop
C. Julier
Author Affiliation
Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.
Source
Am J Hum Genet. 1997 Jan;60(1):174-87
Date
Jan-1997
Language
English
Publication Type
Article
Keywords
Adult
Age of Onset
Chromosomes, Human, Pair 6
Diabetes Mellitus, Type 1 - genetics
Female
Genetic Predisposition to Disease
HLA Antigens - genetics
Humans
Linkage (Genetics)
Major Histocompatibility Complex
Male
Microsatellite Repeats
Sex Characteristics
Abstract
Linkage studies have led to the identification of several chromosome regions that may contain susceptibility loci to type I diabetes (IDDM), in addition to the HLA and INS loci. These include two on chromosome 6q, denoted IDDM5 and IDDM8, that are not linked to HLA. In a previous study, we noticed that the evidence for linkage to IDDM susceptibility around the HLA locus extended over a total distance of 100 cM, which suggested to us that another susceptibility locus could reside near HLA. We developed a statistical method to test this hypothesis in a panel of 523 multiplex families from France, the United States, and Denmark (a total of 667 affected sib pairs, 536 with both parents genotyped), and here present evidence (P = .00003) of a susceptibility locus for IDDM located 32 cM from HLA in males but not linked to HLA in females and distinct from IDDM5 and IDDM8. A new statistical method to test for the presence of a second susceptibility locus linked to a known first susceptibility locus (here HLA) is presented. In addition, we analyzed our current family panel with markers for IDDM5 and IDDM8 on chromosome 6 and found suggestions of linkage for both of these loci (P = .002 and .004, respectively, on the complete family panel). When cumulated with previously published results, with overlapping families removed, the affected-sib-pair tests had a significance of P = .0001 for IDDM5 and P = .00004 for IDDM8.
PubMed ID
8981961 View in PubMed
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The genetic locus for free sialic acid storage disease maps to the long arm of chromosome 6.

https://arctichealth.org/en/permalink/ahliterature218030
Source
Am J Hum Genet. 1994 Jun;54(6):1042-9
Publication Type
Article
Date
Jun-1994
Author
L. Haataja
J. Schleutker
A P Laine
M. Renlund
M L Savontaus
C. Dib
J. Weissenbach
L. Peltonen
P. Aula
Author Affiliation
Department of Medical Genetics, University of Turku, Findland.
Source
Am J Hum Genet. 1994 Jun;54(6):1042-9
Date
Jun-1994
Language
English
Publication Type
Article
Keywords
Alleles
Child
Chromosome Mapping
Chromosomes, Human, Pair 6
Female
Finland
Genetic markers
Humans
Linkage Disequilibrium
Lysosomal Storage Diseases - ethnology - genetics
Male
Parents
Pedigree
Polymorphism, Genetic
Sialic Acids - metabolism
Abstract
Salla disease (SD), or adult-type free sialic acid storage disease, is an autosomal recessive lysosomal storage disorder characterized by impaired transport of free sialic acid across the lysosomal membrane and severe psychomotor retardation. Random linkage analysis of a sample of 27 Finnish families allowed us to localize the SD locus to the long arm of chromosome 6. The highest lod score of 8.95 was obtained with a microsatellite marker of locus D6S286 at theta = .00. Evidence for linkage disequilibrium was observed between the SD locus and the alleles of three closely linked markers, suggesting that the length of the critical region for the SD locus is in the order of 190 kb.
Notes
Cites: Biochem Biophys Res Commun. 1977 Dec 21;79(4):1136-41603649
Cites: Genomics. 1991 Jun;10(2):333-72071142
Cites: J Neurochem. 1982 Mar;38(3):803-97057193
Cites: Proc Natl Acad Sci U S A. 1982 Aug;79(15):4535-96812049
Cites: Neurology. 1983 Jan;33(1):57-666681560
Cites: Eur J Pediatr. 1982 Oct;139(2):142-77151835
Cites: J Pediatr. 1984 Feb;104(2):232-66694015
Cites: Proc Natl Acad Sci U S A. 1984 Jun;81(11):3443-66587361
Cites: Hum Genet. 1991 Nov;88(1):95-71959930
Cites: Hum Genet. 1992 Jan;88(3):298-3001733832
Cites: Dev Neurosci. 1991;13(4-5):327-301817039
Cites: Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6609-131631163
Cites: Nature. 1992 Oct 29;359(6398):794-8011436057
Cites: Genomics. 1993 Jan;15(1):225-78432543
Cites: J Med Genet. 1993 Apr;30(4):265-88487268
Cites: Genomics. 1993 Jun;16(3):720-58325646
Cites: Genomics. 1993 Sep;17(3):694-88244386
Cites: Nat Genet. 1992 Nov;2(3):204-111345170
Cites: Eur J Hum Genet. 1993;1(2):125-327914464
Cites: Nat Genet. 1993 Apr;3(4):338-417981754
Cites: J Med Genet. 1984 Jun;21(3):164-726086927
Cites: Science. 1986 May 9;232(4751):759-623961501
Cites: Prenat Diagn. 1986 Nov-Dec;6(6):437-463809113
Cites: J Med Genet. 1987 Sep;24(9):539-433669048
Cites: Am J Med Genet. 1987 Oct;28(2):377-843425617
Cites: Hum Genet. 1988 Dec;80(4):317-212904399
Cites: J Biol Chem. 1989 Sep 15;264(26):15247-542768261
Cites: J Clin Invest. 1991 Apr;87(4):1329-352010546
Cites: J Biol Chem. 1991 Apr 25;266(12):7456-612019577
Cites: Arch Neurol. 1979 Feb;36(2):88-94420628
PubMed ID
8198127 View in PubMed
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Genome-wide search for linkage of bipolar affective disorders in a very large pedigree derived from a homogeneous population in quebec points to a locus of major effect on chromosome 12q23-q24.

https://arctichealth.org/en/permalink/ahliterature200822
Source
Am J Med Genet. 1999 Oct 15;88(5):567-87
Publication Type
Article
Date
Oct-15-1999
Author
J. Morissette
A. Villeneuve
L. Bordeleau
D. Rochette
C. Laberge
B. Gagné
C. Laprise
G. Bouchard
M. Plante
L. Gobeil
E. Shink
J. Weissenbach
N. Barden
Author Affiliation
Neuroscience, CHUL Research Center and Laval University, Québec, Canada.
Source
Am J Med Genet. 1999 Oct 15;88(5):567-87
Date
Oct-15-1999
Language
English
Publication Type
Article
Keywords
Bipolar Disorder - genetics
Chromosomes, Human, Pair 12
Chromosomes, Human, Pair 5
Female
Follow-Up Studies
Genetic Heterogeneity
Genetic Linkage
Genetic markers
Genetic Predisposition to Disease
Genetic Testing
Genotype
Haplotypes
Humans
Lod Score
Male
Pedigree
Quebec
Abstract
We completed a genome-wide scan for susceptibility loci for bipolar affective disorders in families derived from a rather homogeneous population in the Province of Québec. The genetic homogeneity of this population stems from the migration of founding families into this relatively isolated area of Québec in the 1830s. A possible founder effect, combined with a prevalence of very large families, makes this population ideal for linkage studies. Genealogies for probands can be readily constructed from a population database of acts of baptism and marriage from the early 1830s up to the present time (the BALSAC register). We chose probands with a DSM III diagnosis of bipolar affective disorder and who may be grouped within large families having genealogical origins with the founding population of the Saguenay-Lac-St-Jean area. Living members (n approximately 120) of a very large pedigree were interviewed using the Structured Clinical Interview for DSM III (SCID I), SCID II, and with a family history questionnaire. A diagnostic panel evaluated multisource information (interview, medical records, family history) and pronounced best-estimate consensus diagnoses on all family members. Linkage, SimAPM, SimIBD, and sib-pair analyses have been performed with 332 microsatellite probes covering the entire genome at an average spacing of 11 cM. GENEHUNTER and haplotype analyses were performed on regions of interest. Analysis of a second large pedigree in the same regions of interest permitted confirmation of presumed linkages found in the region of chromosome 12q23-q24.
PubMed ID
10490718 View in PubMed
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Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13.

https://arctichealth.org/en/permalink/ahliterature47694
Source
Nat Genet. 2001 Aug;28(4):365-70
Publication Type
Article
Date
Aug-2001
Author
J. Magré
M. Delépine
E. Khallouf
T. Gedde-Dahl
L. Van Maldergem
E. Sobel
J. Papp
M. Meier
A. Mégarbané
A. Bachy
A. Verloes
F H d'Abronzo
E. Seemanova
R. Assan
N. Baudic
C. Bourut
P. Czernichow
F. Huet
F. Grigorescu
M. de Kerdanet
D. Lacombe
P. Labrune
M. Lanza
H. Loret
F. Matsuda
J. Navarro
A. Nivelon-Chevalier
M. Polak
J J Robert
P. Tric
N. Tubiana-Rufi
C. Vigouroux
J. Weissenbach
S. Savasta
J A Maassen
O. Trygstad
P. Bogalho
P. Freitas
J L Medina
F. Bonnicci
B I Joffe
G. Loyson
V R Panz
F J Raal
S. O'Rahilly
T. Stephenson
C R Kahn
M. Lathrop
J. Capeau
Author Affiliation
INSERM U.402, Faculté de Médecine Saint-Antoine, Université Pierre et Marie Curie, 27 rue Chaligny, 75012 Paris, France. magre@st-antoine.inserm.fr
Source
Nat Genet. 2001 Aug;28(4):365-70
Date
Aug-2001
Language
English
Publication Type
Article
Keywords
Acanthosis Nigricans - complications
Chromosomes, Human, Pair 11 - genetics
Chromosomes, Human, Pair 9 - genetics
Cluster analysis
DNA Mutational Analysis
Diabetes Complications
Female
GTP-Binding Protein gamma Subunits
Genes, Recessive
Genetic markers
Genetic Screening
Haplotypes
Hepatomegaly - complications
Heterotrimeric GTP-Binding Proteins - genetics
Humans
Hyperandrogenism - complications
Hypertriglyceridemia - complications
Insulin Resistance - genetics
Lebanon - epidemiology
Linkage (Genetics)
Lipodystrophy - complications - congenital - epidemiology - genetics
Male
Middle Aged
Molecular Sequence Data
Mutation
Norway - epidemiology
Organ Specificity
Pedigree
Protein Structure, Tertiary
Proteins - genetics - metabolism
Research Support, Non-U.S. Gov't
Sequence Homology, Amino Acid
Abstract
Congenital generalized lipodystrophy, or Berardinelli-Seip syndrome (BSCL), is a rare autosomal recessive disease characterized by a near-absence of adipose tissue from birth or early infancy and severe insulin resistance. Other clinical and biological features include acanthosis nigricans, hyperandrogenism, muscular hypertrophy, hepatomegaly, altered glucose tolerance or diabetes mellitus, and hypertriglyceridemia. A locus (BSCL1) has been mapped to 9q34 with evidence of heterogeneity. Here, we report a genome screen of nine BSCL families from two geographical clusters (in Lebanon and Norway). We identified a new disease locus, designated BSCL2, within the 2.5-Mb interval flanked by markers D11S4076 and D11S480 on chromosome 11q13. Analysis of 20 additional families of various ethnic origins led to the identification of 11 families in which the disease cosegregates with the 11q13 locus; the remaining families provide confirmation of linkage to 9q34. Sequence analysis of genes located in the 11q13 interval disclosed mutations in a gene homologous to the murine guanine nucleotide-binding protein (G protein), gamma3-linked gene (Gng3lg) in all BSCL2-linked families. BSCL2 is most highly expressed in brain and testis and encodes a protein (which we have called seipin) of unknown function. Most of the variants are null mutations and probably result in a severe disruption of the protein. These findings are of general importance for understanding the molecular mechanisms underlying regulation of body fat distribution and insulin resistance.
PubMed ID
11479539 View in PubMed
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Linkage disequilibrium analysis in young populations: pseudo-vitamin D-deficiency rickets and the founder effect in French Canadians.

https://arctichealth.org/en/permalink/ahliterature211249
Source
Am J Hum Genet. 1996 Sep;59(3):633-43
Publication Type
Article
Date
Sep-1996
Author
M. Labuda
D. Labuda
M. Korab-Laskowska
D E Cole
E. Zietkiewicz
J. Weissenbach
E. Popowska
E. Pronicka
A W Root
F H Glorieux
Author Affiliation
Genetics Unit, Shriners Hospital for Crippled Children, Montreal, Quebec, Canada.
Source
Am J Hum Genet. 1996 Sep;59(3):633-43
Date
Sep-1996
Language
English
Publication Type
Article
Keywords
Base Sequence
Canada - epidemiology
Chromosome Mapping
Chromosomes, Human, Pair 12 - genetics
Demography
Female
Founder Effect
France - ethnology
Haplotypes
Humans
Linkage Disequilibrium
Male
Molecular Sequence Data
Rickets - ethnology - genetics
Vitamin D Deficiency - ethnology - genetics
Abstract
Pseudo-vitamin D-deficiency rickets (PDDR) was mapped close to D12S90 and between proximal D12S312 and distal (D12S305, D12S104) microsatellites that were subsequently found on a single YAC clone. Analysis of a complex haplotype in linkage disequilibrium (LD) with the disease discriminated among distinct founder effects in French Canadian populations in Acadia and in Charlevoix-Saguenay-Lac-Saint-Jean (Ch-SLSJ), as well as an earlier one in precolonial Europe. A simple demographic model suggested the historical age of the founder effect in Ch-SLSJ to be approximately 12 generations. The corresponding LD data are consistent with this figure when they are analyzed within the framework of Luria-Delbrück model, which takes into account the population growth. Population sampling due to a limited number of first settlers and the rapid demographic expansion appear to have played a major role in the founding of PDDR in Ch-SLSJ and, presumably, other genetic disorders endemic to French Canada. Similarly, the founder effect in Ashkenazim, coinciding with their early settlement in medieval Poland and subsequent expansion eastward, could explain the origin of frequent genetic diseases in this population.
Notes
Cites: J Pediatr. 1981 Jul;99(1):26-346265615
Cites: Am J Hum Genet. 1985 May;37(3):482-983859205
Cites: Science. 1989 Sep 8;245(4922):1073-802570460
Cites: Hum Genet. 1990 Apr;84(5):449-541969843
Cites: Am J Hum Genet. 1990 Jul;47(1):28-361971995
Cites: J Bone Miner Res. 1992 Dec;7(12):1447-531336301
Cites: Hum Mol Genet. 1993 Aug;2(8):1229-348104628
Cites: J Med Genet. 1993 Oct;30(10):857-658230163
Cites: Am J Hum Genet. 1993 Dec;53(6):1279-888250044
Cites: Nature. 1993 Dec 16;366(6456):698-7018259213
Cites: J Bone Miner Res. 1993 Nov;8(11):1397-4068266831
Cites: Nat Genet. 1992 Nov;2(3):204-111345170
Cites: Am J Hum Genet. 1994 Aug;55(2):348-557913583
Cites: Am J Hum Genet. 1994 Sep;55(3):453-608079989
Cites: Nat Genet. 1994 Jun;7(2 Spec No):246-3397545953
Cites: Am J Hum Genet. 1994 Nov;55(5):937-457977356
Cites: Am J Hum Genet. 1995 Mar;56(3):777-877887434
Cites: Am J Hum Genet. 1995 Apr;56(4):970-87717408
Cites: Nat Genet. 1995 Feb;9(2):152-97719342
Cites: Nat Genet. 1995 Feb;9(2):99-1017719352
Cites: Am J Hum Genet. 1995 Jun;56(6):1450-57762568
Cites: Am J Hum Genet. 1996 Mar;58(3):506-128644710
Cites: Am J Hum Genet. 1996 Mar;58(3):523-348644712
Cites: Am J Hum Genet. 1995 Jan;56(1):18-327825575
Cites: Am J Hum Genet. 1995 Mar;56(3):654-627887419
PubMed ID
8751865 View in PubMed
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