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V. I. Vitart, S. MacKay, A. Pyott, B. Fleck, H. Campbell, A. Wright; Mapping of Genetic Variants Underlying High Myopia and High Hypermetropia in the Western Isles of Scotland. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2819.
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© ARVO (1962-2015); The Authors (2016-present)
Our aim is to identify genetic variants underlying high myopia and high hypermetropia using an isolated population: the Western isles of Scotland.
We recruited 152 individuals, local from the Western Isles, with extreme refractive errors via optometrist records or preoperative records from cataract operation theatre. We also recruited their close relatives. The relatedness of index probands was first sought using extensive genealogical records and later assessed by analysis of their genotypes generated using the Affy_5 SNP array. Here we report our preliminary results for 2 of the mapping designs applied: homozygosity mapping and linkage analysis.
Homozygosity mapping: We identified 2 candidate regions overrepresented in the myopic group. The largest overlap,on chromosome 9, was 1.2Mb long (36 SNPs), and shared by 3 homozygous tracts of over 1.4Mb each (4.7Mb,3.4Mb and 1.4Mb) observed only in 3 unrelated high myopic probands . The length of the tracts in these individuals suggests that each was inherited identical-by-descent (IBD). The 3 probands all had a history of wearing corrective glasses at a young age (6years, 6years and 12years). The second largest overlap was ten fold smaller at 130kb (38 SNPs) on chromosome 22 and interestingly represented the overlap of 9 homozygous tracts, including 2 very long (8.2 and 7.5Mb) present only in myopic probands.Linkage analysis: Six families with apparent dominant inheritance of severe hypermetropia were analysed using the software "ALOHOMORA" to prepare a SNP dataset suitable for a downstream linkage analysis using the proprietary software package "Allegro". The largest family,spanning 3 generations, had 19 members typed including 11 affected members. A first round of analysis using parametric linkage analysis revealed 2 candidate regions of multipoint linkage with heterogeneity LOD scores greater than 2. Scores for the families taken individually revealed that the first region, on chr4, reached statistical significance with a LOD score of 3.3 in the largest family analysed. The other signal, on chr11, is due mainly to another individual family.
The preliminary results suggest diversity even in an isolated population and may give a handle on mapping rare alleles of strong effect underlying severe refractive errors, which association studies will not find. Homozygosity mapping is ideally suited in this population where many remote inbreeding loops were observed in the genealogy trees.
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