title: North Carolina macular dystrophy (MCDR1) locus: a fine resolution genetic map and haplotype analysis.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Ophthalmology, the Jules Stein Eye Institute, University of California, Los Angeles, CA 90095, USA. small@jsei.ucla.edu
authors.forename: K W
authors.initials: KW
authors.lastname: Small
authors.forename: N
authors.initials: N
authors.lastname: Udar
authors.forename: S
authors.initials: S
authors.lastname: Yelchits
authors.forename: R
authors.initials: R
authors.lastname: Klein
authors.forename: C
authors.initials: C
authors.lastname: Garcia
authors.forename: G
authors.initials: G
authors.lastname: Gallardo
authors.forename: B
authors.initials: B
authors.lastname: Puech
authors.forename: V
authors.initials: V
authors.lastname: Puech
authors.forename: D
authors.initials: D
authors.lastname: Saperstein
authors.forename: J
authors.initials: J
authors.lastname: Lim
authors.forename: J
authors.initials: J
authors.lastname: Haller
authors.forename: C
authors.initials: C
authors.lastname: Flaxel
authors.forename: R
authors.initials: R
authors.lastname: Kelsell
authors.forename: D
authors.initials: D
authors.lastname: Hunt
authors.forename: K
authors.initials: K
authors.lastname: Evans
authors.forename: F
authors.initials: F
authors.lastname: Lennon
authors.forename: M
authors.initials: M
authors.lastname: Pericak-Vance
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002896:Chromosomes, Human, Pair 6; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008126:Lod Score; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction
chemical_list: D005136:Eye Proteins; D005819:Genetic Markers; C402686:MCDR1 protein, human