Homozygosity mapping of achromatopsia to chromosome 2 using DNA pooling

Nancy C Arbour; J Zlotogora; R G Knowlton; Saul Merin; A Rosenmann; Adam B Kanis; Tatiana Rokhlina; Edwin M Stone; Val C Sheffield

doi:10.1093/hmg/6.5.689

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Homozygosity mapping of achromatopsia to chromosome 2 using DNA pooling

Journal article

Open access

Peer reviewed

Homozygosity mapping of achromatopsia to chromosome 2 using DNA pooling

Nancy C Arbour, J Zlotogora, R G Knowlton, Saul Merin, A Rosenmann, Adam B Kanis, Tatiana Rokhlina, Edwin M Stone and Val C Sheffield

Human molecular genetics, Vol.6(5), pp.689-694

05/1997

DOI: 10.1093/hmg/6.5.689

PMID: 9158143

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Abstract

Achromatopsia is an autosomal recessive disease of the retina, characterized clinically by an inability to distinguish colors, impaired visual acuity, nystagmus and photophobia. A genome-wide search for linkage was performed using an inbred Jewish kindred from Iran. To facilitate the genome-wide search, we utilized a DNA pooling strategy which takes advantage of the likelihood that the disease in this inbred kindred is inherited by all affected individuals from a common founder. Equal molar amounts of DNA from all affected individuals were pooled and used as the PCR template for short tandem repeat polymorphic markers (STRPs). Pooled DNA from unaffected members of the kindred was used as a control. A reduction in the number of alleles in the affected versus control pool was observed at several loci. Upon genotyping of individual family members, significant linkage was established between the disease phenotype and markers localized on chromosome 2. The highest LOD score observed was 5.4 (theta = 0). When four additional small unrelated families were genotyped, the combined peak LOD score was 8.2. Analysis of recombinant chromosomes revealed that the disease gene lies within a 30 cM interval which spans the centromere. Additional fine-mapping studies identified a region of homozygosity in all affected individuals, narrowing the region to 14 cM. A candidate gene for achromatopsia was excluded from this disease interval by radiation hybrid mapping. Linkage of achromatopsia to chromosome 2 is an essential first step in the identification of the disease-causing gene.

Genetic Markers

Humans

Nystagmus, Pathologic - genetics

Male

Nerve Tissue Proteins - genetics

Color Vision Defects - genetics

Jews - genetics

Polymorphism, Genetic

Chromosomes, Human, Pair 2

Founder Effect

Homozygote

Pedigree

Chromosome Mapping - methods

Chromosomes, Human, Pair 14

Female

Iran - ethnology

Genetic Linkage

Details

Title: Subtitle: Homozygosity mapping of achromatopsia to chromosome 2 using DNA pooling
Creators: Nancy C Arbour - Department of Pediatrics, University of Iowa, Iowa City 52242, USA
J Zlotogora
R G Knowlton
Saul Merin
A Rosenmann
Adam B Kanis
Tatiana Rokhlina
Edwin M Stone
Val C Sheffield
Resource Type: Journal article
Publication Details: Human molecular genetics, Vol.6(5), pp.689-694
DOI: 10.1093/hmg/6.5.689
PMID: 9158143
NLM abbreviation: Hum Mol Genet
ISSN: 0964-6906
eISSN: 1460-2083
Publisher: England
Grant note: HG00457 / NHGRI NIH HHS
Language: English
Date published: 05/1997
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
Record Identifier: 9983980020602771

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