North Carolina macular dystrophy (MCDR1) locus

a fine resolution genetic map and haplotype analysis.

K. W. Small, N. Udar, S. Yelchits, R. Klein, C. Garcia, G. Gallardo, B. Puech, V. Puech, D. Saperstein, J. Lim, J. Haller, Christina Flaxel, R. Kelsell, D. Hunt, K. Evans, F. Lennon, M. Pericak-Vance

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

PURPOSE: We previously reported linkage of North Carolina macular dystrophy in a single isolated family to a broad region on chromosome 6q16. In order to refine the localization of the MCDR1 gene (North Carolina macular dystrophy), additional families with this disease and new markers were studied. METHODS: We ascertained 10 families with the North Carolina macular dystrophy phenotype (MCDR1). These families were of various ethnic and geographic origins such as Caucasian, Mayan Indian, African-American, French, British, German, and American of European decent. Two hundred thirty-two individuals in these families underwent comprehensive ophthalmic examinations and blood was collected for genotyping. One hundred seventeen were found to be affected. Linkage simulation studies were performed. Two-point linkage, haplotype analysis, and multipoint linkage was performed using VITESSE and FASTLINK. HOMOG was used to test for genetic heterogeneity. RESULTS: The clinical features were consistent with the diagnosis of North Carolina macular dystrophy in all families. Multipoint linkage analysis indicates that the MCDR1 gene is in the interval between D6D249 and D6S1671 with a maximum LOD score of 41.52. There was no evidence of genetic heterogeneity among the families studied. Families 765, 768, 772, 1193, and 1292 shared the same chromosomal haplotype in this region. CONCLUSIONS: This is the largest single data set of families with the MCDR1 phenotype. The single large family from North Carolina continues to be informative for the closest flanking markers and alone supports the minimal candidate region as suggested by previous studies. There remains no evidence of genetic heterogeneity in this disease. Most of the American families appear to have descended from the same ancestral mutation. The remaining families could each represent independent origins of the mutation in the MCDR1 gene.

Original languageEnglish (US)
Pages (from-to)38
Number of pages1
JournalMolecular vision [electronic resource]
Volume5
StatePublished - Dec 29 1999
Externally publishedYes

Fingerprint

Haplotypes
Genetic Heterogeneity
Macular dystrophy, retinal, 1, North Carolina type
Genes
Phenotype
Mutation
African Americans
Chromosomes

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Small, K. W., Udar, N., Yelchits, S., Klein, R., Garcia, C., Gallardo, G., ... Pericak-Vance, M. (1999). North Carolina macular dystrophy (MCDR1) locus: a fine resolution genetic map and haplotype analysis. Molecular vision [electronic resource], 5, 38.

North Carolina macular dystrophy (MCDR1) locus : a fine resolution genetic map and haplotype analysis. / Small, K. W.; Udar, N.; Yelchits, S.; Klein, R.; Garcia, C.; Gallardo, G.; Puech, B.; Puech, V.; Saperstein, D.; Lim, J.; Haller, J.; Flaxel, Christina; Kelsell, R.; Hunt, D.; Evans, K.; Lennon, F.; Pericak-Vance, M.

In: Molecular vision [electronic resource], Vol. 5, 29.12.1999, p. 38.

Research output: Contribution to journalArticle

Small, KW, Udar, N, Yelchits, S, Klein, R, Garcia, C, Gallardo, G, Puech, B, Puech, V, Saperstein, D, Lim, J, Haller, J, Flaxel, C, Kelsell, R, Hunt, D, Evans, K, Lennon, F & Pericak-Vance, M 1999, 'North Carolina macular dystrophy (MCDR1) locus: a fine resolution genetic map and haplotype analysis.', Molecular vision [electronic resource], vol. 5, pp. 38.
Small, K. W. ; Udar, N. ; Yelchits, S. ; Klein, R. ; Garcia, C. ; Gallardo, G. ; Puech, B. ; Puech, V. ; Saperstein, D. ; Lim, J. ; Haller, J. ; Flaxel, Christina ; Kelsell, R. ; Hunt, D. ; Evans, K. ; Lennon, F. ; Pericak-Vance, M. / North Carolina macular dystrophy (MCDR1) locus : a fine resolution genetic map and haplotype analysis. In: Molecular vision [electronic resource]. 1999 ; Vol. 5. pp. 38.
@article{3d799c11883e4ca3a80590e944e5f242,
title = "North Carolina macular dystrophy (MCDR1) locus: a fine resolution genetic map and haplotype analysis.",
abstract = "PURPOSE: We previously reported linkage of North Carolina macular dystrophy in a single isolated family to a broad region on chromosome 6q16. In order to refine the localization of the MCDR1 gene (North Carolina macular dystrophy), additional families with this disease and new markers were studied. METHODS: We ascertained 10 families with the North Carolina macular dystrophy phenotype (MCDR1). These families were of various ethnic and geographic origins such as Caucasian, Mayan Indian, African-American, French, British, German, and American of European decent. Two hundred thirty-two individuals in these families underwent comprehensive ophthalmic examinations and blood was collected for genotyping. One hundred seventeen were found to be affected. Linkage simulation studies were performed. Two-point linkage, haplotype analysis, and multipoint linkage was performed using VITESSE and FASTLINK. HOMOG was used to test for genetic heterogeneity. RESULTS: The clinical features were consistent with the diagnosis of North Carolina macular dystrophy in all families. Multipoint linkage analysis indicates that the MCDR1 gene is in the interval between D6D249 and D6S1671 with a maximum LOD score of 41.52. There was no evidence of genetic heterogeneity among the families studied. Families 765, 768, 772, 1193, and 1292 shared the same chromosomal haplotype in this region. CONCLUSIONS: This is the largest single data set of families with the MCDR1 phenotype. The single large family from North Carolina continues to be informative for the closest flanking markers and alone supports the minimal candidate region as suggested by previous studies. There remains no evidence of genetic heterogeneity in this disease. Most of the American families appear to have descended from the same ancestral mutation. The remaining families could each represent independent origins of the mutation in the MCDR1 gene.",
author = "Small, {K. W.} and N. Udar and S. Yelchits and R. Klein and C. Garcia and G. Gallardo and B. Puech and V. Puech and D. Saperstein and J. Lim and J. Haller and Christina Flaxel and R. Kelsell and D. Hunt and K. Evans and F. Lennon and M. Pericak-Vance",
year = "1999",
month = "12",
day = "29",
language = "English (US)",
volume = "5",
pages = "38",
journal = "Molecular Vision",
issn = "1090-0535",

}

TY - JOUR

T1 - North Carolina macular dystrophy (MCDR1) locus

T2 - a fine resolution genetic map and haplotype analysis.

AU - Small, K. W.

AU - Udar, N.

AU - Yelchits, S.

AU - Klein, R.

AU - Garcia, C.

AU - Gallardo, G.

AU - Puech, B.

AU - Puech, V.

AU - Saperstein, D.

AU - Lim, J.

AU - Haller, J.

AU - Flaxel, Christina

AU - Kelsell, R.

AU - Hunt, D.

AU - Evans, K.

AU - Lennon, F.

AU - Pericak-Vance, M.

PY - 1999/12/29

Y1 - 1999/12/29

N2 - PURPOSE: We previously reported linkage of North Carolina macular dystrophy in a single isolated family to a broad region on chromosome 6q16. In order to refine the localization of the MCDR1 gene (North Carolina macular dystrophy), additional families with this disease and new markers were studied. METHODS: We ascertained 10 families with the North Carolina macular dystrophy phenotype (MCDR1). These families were of various ethnic and geographic origins such as Caucasian, Mayan Indian, African-American, French, British, German, and American of European decent. Two hundred thirty-two individuals in these families underwent comprehensive ophthalmic examinations and blood was collected for genotyping. One hundred seventeen were found to be affected. Linkage simulation studies were performed. Two-point linkage, haplotype analysis, and multipoint linkage was performed using VITESSE and FASTLINK. HOMOG was used to test for genetic heterogeneity. RESULTS: The clinical features were consistent with the diagnosis of North Carolina macular dystrophy in all families. Multipoint linkage analysis indicates that the MCDR1 gene is in the interval between D6D249 and D6S1671 with a maximum LOD score of 41.52. There was no evidence of genetic heterogeneity among the families studied. Families 765, 768, 772, 1193, and 1292 shared the same chromosomal haplotype in this region. CONCLUSIONS: This is the largest single data set of families with the MCDR1 phenotype. The single large family from North Carolina continues to be informative for the closest flanking markers and alone supports the minimal candidate region as suggested by previous studies. There remains no evidence of genetic heterogeneity in this disease. Most of the American families appear to have descended from the same ancestral mutation. The remaining families could each represent independent origins of the mutation in the MCDR1 gene.

AB - PURPOSE: We previously reported linkage of North Carolina macular dystrophy in a single isolated family to a broad region on chromosome 6q16. In order to refine the localization of the MCDR1 gene (North Carolina macular dystrophy), additional families with this disease and new markers were studied. METHODS: We ascertained 10 families with the North Carolina macular dystrophy phenotype (MCDR1). These families were of various ethnic and geographic origins such as Caucasian, Mayan Indian, African-American, French, British, German, and American of European decent. Two hundred thirty-two individuals in these families underwent comprehensive ophthalmic examinations and blood was collected for genotyping. One hundred seventeen were found to be affected. Linkage simulation studies were performed. Two-point linkage, haplotype analysis, and multipoint linkage was performed using VITESSE and FASTLINK. HOMOG was used to test for genetic heterogeneity. RESULTS: The clinical features were consistent with the diagnosis of North Carolina macular dystrophy in all families. Multipoint linkage analysis indicates that the MCDR1 gene is in the interval between D6D249 and D6S1671 with a maximum LOD score of 41.52. There was no evidence of genetic heterogeneity among the families studied. Families 765, 768, 772, 1193, and 1292 shared the same chromosomal haplotype in this region. CONCLUSIONS: This is the largest single data set of families with the MCDR1 phenotype. The single large family from North Carolina continues to be informative for the closest flanking markers and alone supports the minimal candidate region as suggested by previous studies. There remains no evidence of genetic heterogeneity in this disease. Most of the American families appear to have descended from the same ancestral mutation. The remaining families could each represent independent origins of the mutation in the MCDR1 gene.

UR - http://www.scopus.com/inward/record.url?scp=0033616054&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033616054&partnerID=8YFLogxK

M3 - Article

VL - 5

SP - 38

JO - Molecular Vision

JF - Molecular Vision

SN - 1090-0535

ER -