Genetic linkage study of high-grade myopia in a Hutterite population from South Dakota

Division of Ophthalmology, Children's Hospital of Philadelphia, Philadelphia, PA, USA. <>
Molecular vision (Impact Factor: 1.99). 02/2007; 13:229-36.
Source: PubMed


Myopia is a common, complex disorder, and severe forms have implications for blindness due to increased risk of premature cataracts, glaucoma, retinal detachment, and macular degeneration. Autosomal dominant (AD) non-syndromic high-grade myopia has been mapped to chromosomes 18p11.31, 12q21-23, 17q21-23, 7q36, 2q37.1, 7p15.3, 15q12-13, 3q26, 4q12, 8p23, 4q22-q27, 1p36, and Xq23-q25. Here, we demonstrate evidence of linkage for AD non-syndromic high-grade myopia in a large Hutterite family to a locus on chromosome 10q21.1.
After clinical evaluation, genomic DNA was genotyped from 29 members of a Hutterite family from South Dakota (7 affected). The average refractive error of affected individuals was -7.04 diopters. Microsatellite markers were used to exclude linkage to the known AD nonsyndromic high-grade myopia loci as well as to syndromic high-grade myopia loci. A genome screen was then performed using 382 markers with an average inter-marker distance of 10 cM followed by fine-point mapping in all regions of the genome that gave positive LOD scores. SimWalk2 software was used for multipoint linkage based on AD and autosomal recessive (AR) models with a penetrance of 90% and a disease allele frequency of 0.001.
A maximum multipoint LOD score of 3.22 was achieved under an AD model at microsatellite marker D10S1643. Fine point mapping and haplotype analysis defined a critical region of 2.67 cM on chromosome 10q21.1. Haplotype analysis demonstrated two distinct haplotypes segregating with high-grade myopia, indicative of two distinct mutations occurring in the same gene.
We have identified a presumptive myopia locus for high-grade myopia based on linkage and haplotype analysis.

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    • "Young et al. [17] États-Unis (EU) MYP3 12q21-23 Young et al. [18] Italie/Allemagne MYP4 7q36 Naiglin et al. [19] France MYP5 17q21-q22 Paluru et al. [20] Angleterre/Canada MYP11 4q22-q27 Zhang et al. [21] Chine MYP12 2q37.1 Paluru et al. [22] Europe du Nord MYP13 Xq23-q27.2 Zhang et al. [21] [23] Chine — ethnie Han MYP15 10q21.1 Nallasamy et al. [24] Comm. huttérite (EU) — 15q12-13 Yu et al. [25] Chine MYP16 5p15.33-p15.2 "
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