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Identification of a locus for autosomal dominant high myopia on chromosome 5p13.3-p15.1 in a Chinese family.

Ma JH, Shen SH, Zhang GW, Zhao DS, Xu C, Pan CM, Jiang H, Wang ZQ, Song HD - Mol. Vis. (2010)

Bottom Line: The genome-wide screening identified a maximum two-point LOD score of 3.71 at θ=0.00 with the microsatellite marker D5S502.Fine mapping and haplotype analysis defined a critical region of 11.69 cM between D5S2096 and D5S1986 on chromosome 5p13.3-p15.1.Sequence analysis of the candidate genes inside the linked region did not identify any causative mutations.

View Article: PubMed Central - PubMed

Affiliation: Ruijin Hospital, State Key Laboratory of Medical Genomics, Shanghai Institute of Endocrinology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

ABSTRACT

Purpose: Myopia and its extreme form, high myopia, are common vision disorders worldwide, especially in Asia. Identifying genetic markers is a useful step toward understanding the genetic basis of high myopia, particularly in the Chinese population, where it is highly prevalent. This study was conducted to provide evidence of linkage for autosomal dominant high myopia to a locus on chromosome 5p13.3-p15.1 in a large Chinese family.

Methods: After clinical evaluation, genomic DNA from 29 members of this family was genotyped. A genome-wide screen was then performed using 382 markers with an average inter-marker distance of 10 cM, and two-point linkage was analyzed using the MLINK program. Mutation analysis of the candidate genes was performed using direct sequencing.

Results: Linkage to the known autosomal dominant high myopia loci was excluded. The genome-wide screening identified a maximum two-point LOD score of 3.71 at θ=0.00 with the microsatellite marker D5S502. Fine mapping and haplotype analysis defined a critical region of 11.69 cM between D5S2096 and D5S1986 on chromosome 5p13.3-p15.1. Sequence analysis of the candidate genes inside the linked region did not identify any causative mutations.

Conclusions: A genetic locus was mapped to chromosome 5p13.3-p15.1 in a large Chinese family with autosomal dominant high myopia.

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Related in: MedlinePlus

Pedigree and haplotype diagram of the family. Circles and squares denote females and males, respectively; blackened symbols denote affected individuals; a diagonal line through a symbol means that the individual is deceased. Haplotypes were constructed on the basis of the minimum number of recombinations between these markers. Solid bar: the chromosome assumed to carry the inherited disease allele; open bar: normal haplotypes. Only essential members are shown; nonparticipating family members were excluded. For individuals IV:2, only one set of parental-allele information was available; therefore, the genotype information was indeterminate (denoted by question marks) for markers D5S416 and D5S385. Individual III:17 was recombinant for the telomeric marker D5S2096. Individuals III:7 and III:11 were recombinant for the centromeric marker D5S1986.
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f1: Pedigree and haplotype diagram of the family. Circles and squares denote females and males, respectively; blackened symbols denote affected individuals; a diagonal line through a symbol means that the individual is deceased. Haplotypes were constructed on the basis of the minimum number of recombinations between these markers. Solid bar: the chromosome assumed to carry the inherited disease allele; open bar: normal haplotypes. Only essential members are shown; nonparticipating family members were excluded. For individuals IV:2, only one set of parental-allele information was available; therefore, the genotype information was indeterminate (denoted by question marks) for markers D5S416 and D5S385. Individual III:17 was recombinant for the telomeric marker D5S2096. Individuals III:7 and III:11 were recombinant for the centromeric marker D5S1986.

Mentions: A large family with autosomal dominant high myopia was identified in Zhejiang province, China. This family contained 11 affected individuals over four generations. Participating in this study were 29 individuals (aged 11 to 80 years): 10 affected and 19 unaffected (Figure 1). The study conformed to the guidelines involving human research as stated in the Declaration of Helsinki. Informed consent was obtained from every subject after an explanation of the nature, procedures and possible consequences of the study. This family was chosen based on the presence of numerous male and female family members and successful multiple generations with high myopia, suggesting an autosomal dominant mode of inheritance. Individuals with a spherical refractive error equal to or lower than −6.00 D, axial length longer than 26 mm in at least one eye and a history of myopia onset before 12 years of age were considered affected. Ophthalmology examination was performed for all of the members. No participant had any known ocular disease or insult that could predispose to myopia, such as a history of retinopathy of premature or neonatal problems, or a known genetic disease or connective tissue disorder associated with myopia, such as Stickler or Marfan syndrome. The results of the ophthalmic examinations are summarized in Table 1.


Identification of a locus for autosomal dominant high myopia on chromosome 5p13.3-p15.1 in a Chinese family.

Ma JH, Shen SH, Zhang GW, Zhao DS, Xu C, Pan CM, Jiang H, Wang ZQ, Song HD - Mol. Vis. (2010)

Pedigree and haplotype diagram of the family. Circles and squares denote females and males, respectively; blackened symbols denote affected individuals; a diagonal line through a symbol means that the individual is deceased. Haplotypes were constructed on the basis of the minimum number of recombinations between these markers. Solid bar: the chromosome assumed to carry the inherited disease allele; open bar: normal haplotypes. Only essential members are shown; nonparticipating family members were excluded. For individuals IV:2, only one set of parental-allele information was available; therefore, the genotype information was indeterminate (denoted by question marks) for markers D5S416 and D5S385. Individual III:17 was recombinant for the telomeric marker D5S2096. Individuals III:7 and III:11 were recombinant for the centromeric marker D5S1986.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2965568&req=5

f1: Pedigree and haplotype diagram of the family. Circles and squares denote females and males, respectively; blackened symbols denote affected individuals; a diagonal line through a symbol means that the individual is deceased. Haplotypes were constructed on the basis of the minimum number of recombinations between these markers. Solid bar: the chromosome assumed to carry the inherited disease allele; open bar: normal haplotypes. Only essential members are shown; nonparticipating family members were excluded. For individuals IV:2, only one set of parental-allele information was available; therefore, the genotype information was indeterminate (denoted by question marks) for markers D5S416 and D5S385. Individual III:17 was recombinant for the telomeric marker D5S2096. Individuals III:7 and III:11 were recombinant for the centromeric marker D5S1986.
Mentions: A large family with autosomal dominant high myopia was identified in Zhejiang province, China. This family contained 11 affected individuals over four generations. Participating in this study were 29 individuals (aged 11 to 80 years): 10 affected and 19 unaffected (Figure 1). The study conformed to the guidelines involving human research as stated in the Declaration of Helsinki. Informed consent was obtained from every subject after an explanation of the nature, procedures and possible consequences of the study. This family was chosen based on the presence of numerous male and female family members and successful multiple generations with high myopia, suggesting an autosomal dominant mode of inheritance. Individuals with a spherical refractive error equal to or lower than −6.00 D, axial length longer than 26 mm in at least one eye and a history of myopia onset before 12 years of age were considered affected. Ophthalmology examination was performed for all of the members. No participant had any known ocular disease or insult that could predispose to myopia, such as a history of retinopathy of premature or neonatal problems, or a known genetic disease or connective tissue disorder associated with myopia, such as Stickler or Marfan syndrome. The results of the ophthalmic examinations are summarized in Table 1.

Bottom Line: The genome-wide screening identified a maximum two-point LOD score of 3.71 at θ=0.00 with the microsatellite marker D5S502.Fine mapping and haplotype analysis defined a critical region of 11.69 cM between D5S2096 and D5S1986 on chromosome 5p13.3-p15.1.Sequence analysis of the candidate genes inside the linked region did not identify any causative mutations.

View Article: PubMed Central - PubMed

Affiliation: Ruijin Hospital, State Key Laboratory of Medical Genomics, Shanghai Institute of Endocrinology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

ABSTRACT

Purpose: Myopia and its extreme form, high myopia, are common vision disorders worldwide, especially in Asia. Identifying genetic markers is a useful step toward understanding the genetic basis of high myopia, particularly in the Chinese population, where it is highly prevalent. This study was conducted to provide evidence of linkage for autosomal dominant high myopia to a locus on chromosome 5p13.3-p15.1 in a large Chinese family.

Methods: After clinical evaluation, genomic DNA from 29 members of this family was genotyped. A genome-wide screen was then performed using 382 markers with an average inter-marker distance of 10 cM, and two-point linkage was analyzed using the MLINK program. Mutation analysis of the candidate genes was performed using direct sequencing.

Results: Linkage to the known autosomal dominant high myopia loci was excluded. The genome-wide screening identified a maximum two-point LOD score of 3.71 at θ=0.00 with the microsatellite marker D5S502. Fine mapping and haplotype analysis defined a critical region of 11.69 cM between D5S2096 and D5S1986 on chromosome 5p13.3-p15.1. Sequence analysis of the candidate genes inside the linked region did not identify any causative mutations.

Conclusions: A genetic locus was mapped to chromosome 5p13.3-p15.1 in a large Chinese family with autosomal dominant high myopia.

Show MeSH
Related in: MedlinePlus