+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Exome genotyping and linkage analysis identifies two novel linked regions and replicates two others for myopia in Ashkenazi Jewish families



Exome genotyping and linkage analysis identifies two novel linked regions and replicates two others for myopia in Ashkenazi Jewish families



Bmc Medical Genetics 20(1): 27



Label="BACKGROUND">Myopia is one of most common eye diseases in the world and affects 1 in 4 Americans. It is a complex disease caused by both environmental and genetics effects; the genetics effects are still not well understood. In this study, we performed genetic linkage analyses on Ashkenazi Jewish families with a strong familial history of myopia to elucidate any potential causal genes.Label="METHODS">Sixty-four extended Ashkenazi Jewish families were previously collected from New Jersey. Genotypes from the Illumina ExomePlus array were merged with prior microsatellite linkage data from these families. Additional custom markers were added for candidate regions reported in literature for myopia or refractive error. Myopia was defined as mean spherical equivalent (MSE) of -1D or worse and parametric two-point linkage analyses (using TwoPointLods) and multi-point linkage analyses (using SimWalk2) were performed as well as collapsed haplotype pattern (CHP) analysis in SEQLinkage and association analyses performed with FBAT and rv-TDT.Label="RESULTS">Strongest evidence of linkage was on 1p36(two-point LOD = 4.47) a region previously linked to refractive error (MYP14) but not myopia. Another genome-wide significant locus was found on 8q24.22 with a maximum two-point LOD score of 3.75. CHP analysis also detected the signal on 1p36, localized to the LINC00339 gene with a maximum HLOD of 3.47, as well as genome-wide significant signals on 7q36.1 and 11p15, which overlaps with the MYP7 locus.Label="CONCLUSIONS">We identified 2 novel linkage peaks for myopia on chromosomes 7 and 8 in these Ashkenazi Jewish families and replicated 2 more loci on chromosomes 1 and 11, one previously reported in refractive error but not myopia in these families and the other locus previously reported in the literature. Strong candidate genes have been identified within these linkage peaks in our families. Targeted sequencing in these regions will be necessary to definitively identify causal variants under these linkage peaks.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 066446518

Download citation: RISBibTeXText

PMID: 30704416

DOI: 10.1186/s12881-019-0752-8


Related references

Genomewide linkage scan for myopia susceptibility loci among Ashkenazi Jewish families shows evidence of linkage on chromosome 22q12. American Journal of Human Genetics 75(3): 448-459, 2004

Genomewide linkage scan for schizophrenia susceptibility loci among Ashkenazi Jewish families shows evidence of linkage on chromosome 10q22. American Journal of Human Genetics 73(3): 601-611, 2003

D.O.5 A combination of linkage analysis and exome sequencing identifies a new gene for X-linked CharcotMarieTooth neuropathy. Neuromuscular Disorders 22(9-10): 806-807, 2012

Genomewide linkage scan for bipolar-disorder susceptibility loci among Ashkenazi Jewish families. American Journal of Human Genetics 75(2): 204-219, 2004

A combination of linkage analysis and exome sequencing identifies a new gene for X-linked Charcot–Marie–Tooth neuropathy. 2012

Genomewide scan in Ashkenazi Jewish families demonstrates evidence of linkage of ocular refraction to a QTL on chromosome 1p36. Human Genetics 119(4): 389-399, 2006

Fine-mapping and further localization of schizophrenia susceptibility loci from a genome-wide linkage scan among Ashkenazi Jewish families. American Journal of Human Genetics 73(5): 491, 2003

Evidence for linkage of the gene causing familial Mediterranean fever to chromosome 17q in non-Ashkenazi Jewish families: Second locus or type I error?. Human Genetics 91(6): 527-534, 1993

Two candidate regions for schizophrenia and bipolar disorder on chromosome 18 Linkage and association studies in Ashkenazi Jewish family samples. American Journal of Human Genetics 67(4 Suppl. 2): 330, 2000

Dissecting the genetic heterogeneity of myopia susceptibility in an Ashkenazi Jewish population using ordered subset analysis. Molecular Vision 17: 1641-1651, 2011

High-density SNP analysis of 642 Caucasian families with rheumatoid arthritis identifies two new linkage regions on 11p12 and 2q33. Genes and Immunity 7(4): 277-286, 2006

Genome-wide scan of additional Jewish families confirms linkage of a myopia susceptibility locus to chromosome 22q12. Molecular Vision 12: 1499-1505, 2006

Dense genome-wide SNP linkage scan in 301 hereditary prostate cancer families identifies multiple regions with suggestive evidence for linkage. Human Molecular Genetics 18(10): 1839-1848, 2009

Genetic counseling in Ashkenazi Jewish families with deafness Connexin 26 gene mutation analysis. American Journal of Human Genetics 65(4): A12, 1999

An SNP linkage scan identifies significant Crohn's disease loci on chromosomes 13q13.3 and, in Jewish families, on 1p35.2 and 3q29. Genes and Immunity 9(2): 161-167, 2008