טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentSela-Goldberg Adi
SubjectMapping the Gene for Hereditary Microphthalmia
DepartmentDepartment of Medicine
Supervisor Clinical Professor Ruth Gershoni-Baruch


Abstract

Anophthalmia/microphthalmia are serious eye malformations leading to congenital blindness. Isolated human microphthalmia/anophthalmia is a clinically and genetically heterogeneous eye disorder, ranging from a small sized single eye to complete bilateral absence of ocular tissues. Isolated microphthalmia may be inherited as an autosomal dominant, autosomal recessive, or X-linked trait.  The objective of this study was to map the human microphthalmia locus gene in an inbred Israeli Moslem Arab kindred with congenital microphthalmia by linkage analysis using the homozigosity by descent strategy. Eight affected children (5 boys and 3 girls), from three nuclear families, all products of consanguineous matings, were available for study. The pedigree being consistent with autosomal recessive inheritance and assuming a founder effect, the family was considered optimal for gene mapping using the homozigosity by descent strategy.      Blood samples were donated by 8 individuals with congenital microphtalmia and 11 first degree family members, including  6 obligatory heterozygotes (parents) and 5 sibs, after informed consent from family members or gardians. DNA was extracted by standard methods.  Following a futile search for mutations in candidate genes and after performing linkage analysis using polymorphic markers adjacent to genes known to be associated with microphthalmia we performed a conventional homozygosity mapping using 400 polymorphic markers scattered genomewide at 10CM intervals. Homozigosity mapping yielded unconclusive results. It is possible that in our family, congenital microphthalmia was caused by a defect in a novel developmental gene, which we have not been able to locate yet. Homozygosity mapping in consanguineous families - the gold standard for mapping the disease gene may not be 100% effective. Otherwise the possibility that this family harbors two different mutations, although sounding unrealistic should also be considered.