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Title: Genetic dissection of retinitis pigmentosa and most common forms of glaucoma in Punjab province of Pakistan
Authors: Rashid, Muhammad
Keywords: Biotechnology
Issue Date: 2021
Publisher: Government College University, Faisalabad
Abstract: Role of genetics and genetic predisposition play prominent part in eye diseases. Genetic diseases are very common in consanguineous families and are clinically heterogeneous. Pakistan is rich in consanguineous families. Present study was conducted to find genetic determinants of common eye diseases in 25 Pakistani families. Families with multiple affected subjects were enrolled and clinically characterized. DNA was extracted from blood and the families having primary congenital glaucoma (PCG) were screened for CYP1B1, LTBP2 and MYOC variants. Other families were subjected to whole exome sequencing and predicted pathogenic variants were segregated. In silico pathogenicity prediction of novel alleles was done. Evolutionary conservation of amino acids was performed through ClustalW alignments while 3D modeling of proteins was performed through HOPE and Phyre2 programs. A splice region variant thus found in one of the families was checked for its pathogenicity through exon trapping bioassay. No variant was found in LTBP2 and MYOC. 14 variants in different genes were thus found out of which the most common variants were in glaucoma families. Eight variants were found in glaucoma families out of which 6 were present in CYP1B1 with two novel variants. One family had a known deletion variant of LCA5 c.1151delC [p.(Pro384Glnfs*8)] and one family had a missense novel variant c.289A>G [p.(Ile97Val)] of FOXE3. There were 3 novel variants, a missense c.285G>T [p.(Gln85His)] of AIPL1, a nonsense c.1843A>T [p.(Lys615*)] of MERTK and a splice site missense c.669+5G>A of TRPM1 were found in retinitis pigmentosa families. A family of cone rod dystrophy had a novel frame shift variant c.139delC [p.(Pro47Profs*37)] of GUCY2D. All novel reading frame variants were predicted pathogenic by various in silico programs. Splice site variant of TRPM1 was found exon skipping and thus pathogenic through exon trapping bioassay. This study promotes the understanding of genetic basis and pathophysiology of inherited eye diseases and the notion of genetic modifiers. The findings of this study will pave the way of developing genetics tests and genetic counseling protocols for such families. It further invites the experimental pathogenic confirmation of novel alleles and their treatments.
Gov't Doc #: 26082
Appears in Collections:PhD Thesis of All Public / Private Sector Universities / DAIs.

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