Limits...
Fine mapping linkage analysis identifies a novel susceptibility locus for myopia on chromosome 2q37 adjacent to but not overlapping MYP12.

Schäche M, Chen CY, Pertile KK, Richardson AJ, Dirani M, Mitchell P, Baird PN - Mol. Vis. (2009)

Bottom Line: It is a complex trait influenced by both genetic and environmental factors.The disease interval was refined to a 1.83 cM region that is adjacent to rather than overlapping with the MYP12 locus.Subsequent sequencing of all known and hypothetical genes as well as an association study using an independent myopia case-control cohort showed suggestive but not statistically significant association to two intronic SNPs.

View Article: PubMed Central - PubMed

Affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye & Ear Hospital, Melbourne, Australia. mschache@unimelb.edu.au

ABSTRACT

Purpose: Myopia (shortsightedness) is one of the most common ocular conditions worldwide and results in blurred distance vision. It is a complex trait influenced by both genetic and environmental factors. We have previously reported linkage of myopia to a 13.01 cM region of chromosome 2q37 in three large multigenerational Australian families that initially overlapped with the known myopia locus, MYP12. The purpose of this study was to perform fine mapping of this region and identify single nucleotide polymorphisms (SNPs) associated with myopia.

Methods: Fine mapping linkage analysis was performed on three multigenerational families with common myopia to refine the previously mapped critical interval. SNPs in the region were also genotyped to assess for association with myopia using an independent case-control cohort.

Results: The disease interval was refined to a 1.83 cM region that is adjacent to rather than overlapping with the MYP12 locus. Subsequent sequencing of all known and hypothetical genes as well as an association study using an independent myopia case-control cohort showed suggestive but not statistically significant association to two intronic SNPs.

Conclusions: We have identified a novel locus for common myopia on chromosome 2q37.

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Related in: MedlinePlus

Ideogram of human chromosome 2 showing the location of the newly fine mapped region relative to the original linkage region and MYP12. Fine mapping linkage analysis now clearly indicates that the region of interest is adjacent to but does not overlap MYP12.
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f3: Ideogram of human chromosome 2 showing the location of the newly fine mapped region relative to the original linkage region and MYP12. Fine mapping linkage analysis now clearly indicates that the region of interest is adjacent to but does not overlap MYP12.

Mentions: Previous linkage mapping in three myopia families (GEMF0046, GEMF0206, and GEMF0251) identified a 13.01 cM region at 2q37.1 that overlapped with the high myopia locus, MYP12 [39]. A total of 37 myopic and 14 control individuals (including three additional myopic individuals that were not previously available) from these three families were used for fine mapping. Fine mapping of this region resulted in a peak parametric and non-parametric LOD score of 3.97 and 3.48, respectively, at marker D2S338 (Figure 1). This was in agreement with the location of the peak LOD scores reported from our initial genome-wide scan. Haplotype analysis of this region and adjacent regions (6.02 cM proximal and 11.06 cM distal) using 30 polymorphic microsatellite markers at an average spacing of 1.2 cM in the families allowed significant narrowing of the myopia disease gene region (Figure 2). A critical recombination event in individuals 20573, 20580, and 20581 in GEMF0206 (Figure 2A) defined the distal end of the interval to marker D2S2968. A critical recombination event in individuals 20094 and 21490 from GEMF0046 (Figure 2B) and in individuals 21445 and 20472 from GEMF0251 (Figure 2C) defined the proximal end of the refined critical interval to marker D2S1397. The refined interval was identified as a 1.83 cM region on chromosome 2q37.2-2q37.3 that was distal to but did not overlap with the adjacent MYP12 locus (Figure 3).


Fine mapping linkage analysis identifies a novel susceptibility locus for myopia on chromosome 2q37 adjacent to but not overlapping MYP12.

Schäche M, Chen CY, Pertile KK, Richardson AJ, Dirani M, Mitchell P, Baird PN - Mol. Vis. (2009)

Ideogram of human chromosome 2 showing the location of the newly fine mapped region relative to the original linkage region and MYP12. Fine mapping linkage analysis now clearly indicates that the region of interest is adjacent to but does not overlap MYP12.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2666771&req=5

f3: Ideogram of human chromosome 2 showing the location of the newly fine mapped region relative to the original linkage region and MYP12. Fine mapping linkage analysis now clearly indicates that the region of interest is adjacent to but does not overlap MYP12.
Mentions: Previous linkage mapping in three myopia families (GEMF0046, GEMF0206, and GEMF0251) identified a 13.01 cM region at 2q37.1 that overlapped with the high myopia locus, MYP12 [39]. A total of 37 myopic and 14 control individuals (including three additional myopic individuals that were not previously available) from these three families were used for fine mapping. Fine mapping of this region resulted in a peak parametric and non-parametric LOD score of 3.97 and 3.48, respectively, at marker D2S338 (Figure 1). This was in agreement with the location of the peak LOD scores reported from our initial genome-wide scan. Haplotype analysis of this region and adjacent regions (6.02 cM proximal and 11.06 cM distal) using 30 polymorphic microsatellite markers at an average spacing of 1.2 cM in the families allowed significant narrowing of the myopia disease gene region (Figure 2). A critical recombination event in individuals 20573, 20580, and 20581 in GEMF0206 (Figure 2A) defined the distal end of the interval to marker D2S2968. A critical recombination event in individuals 20094 and 21490 from GEMF0046 (Figure 2B) and in individuals 21445 and 20472 from GEMF0251 (Figure 2C) defined the proximal end of the refined critical interval to marker D2S1397. The refined interval was identified as a 1.83 cM region on chromosome 2q37.2-2q37.3 that was distal to but did not overlap with the adjacent MYP12 locus (Figure 3).

Bottom Line: It is a complex trait influenced by both genetic and environmental factors.The disease interval was refined to a 1.83 cM region that is adjacent to rather than overlapping with the MYP12 locus.Subsequent sequencing of all known and hypothetical genes as well as an association study using an independent myopia case-control cohort showed suggestive but not statistically significant association to two intronic SNPs.

View Article: PubMed Central - PubMed

Affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye & Ear Hospital, Melbourne, Australia. mschache@unimelb.edu.au

ABSTRACT

Purpose: Myopia (shortsightedness) is one of the most common ocular conditions worldwide and results in blurred distance vision. It is a complex trait influenced by both genetic and environmental factors. We have previously reported linkage of myopia to a 13.01 cM region of chromosome 2q37 in three large multigenerational Australian families that initially overlapped with the known myopia locus, MYP12. The purpose of this study was to perform fine mapping of this region and identify single nucleotide polymorphisms (SNPs) associated with myopia.

Methods: Fine mapping linkage analysis was performed on three multigenerational families with common myopia to refine the previously mapped critical interval. SNPs in the region were also genotyped to assess for association with myopia using an independent case-control cohort.

Results: The disease interval was refined to a 1.83 cM region that is adjacent to rather than overlapping with the MYP12 locus. Subsequent sequencing of all known and hypothetical genes as well as an association study using an independent myopia case-control cohort showed suggestive but not statistically significant association to two intronic SNPs.

Conclusions: We have identified a novel locus for common myopia on chromosome 2q37.

Show MeSH
Related in: MedlinePlus