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Dielectric Track Detector As a Neutron Dosimeter

Thesis Info

Author

Fariha Malik

Supervisor

Ehsan Ullah Khan

Institute

Allama Iqbal Open University

Institute Type

Public

City

Islamabad

Country

Pakistan

Thesis Completing Year

2004

Thesis Completion Status

Completed

Page

xiv, 97.

Subject

Physics

Language

English

Other

Call No: 539.7 FAD; Publisher: Aiou

Added

2021-02-17 19:49:13

Modified

2023-01-06 19:20:37

ARI ID

1676709915333

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ڈاکٹر صلاح الدین درویش

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IMPLEMENTASI METODE TAMI OTAKA DALAM PEMBELAJARAN HAFALAN AL-QURAN DI TK PINTAR KOTA BANDUNG

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The Genetic Analysis of Retinal Dystrophies in Selected Pakistani Families

THE GENETIC ANALYSIS OF RETINAL DYSTROPHIES IN SELECTED PAKISTANI FAMILIES Retinal Dystrophies (RD) are the major cause of inherited blindness in Pakistan. The worldwide prevalence of RD is 1 in 3,000-5,000 individuals. There are 42 known loci and 154 genes that have been reported to be associated with RD. In Pakistan the percentage of recessive diseases are higher than dominant or X-linked disorders, which might be due to the high level of cousin marriages. Therefore the purpose of the present study was to determine the frequency of the mode of inheritance of RD in the Pakistani population and to evaluate the genetic basis of RD in a cohort of consanguineous families collected from different areas of Pakistan. To determine the inheritance pattern of RD in the Pakistani population, data about medical and family history of 80 families suffering from RD were collected from different areas of Pakistan. Homozygosity mapping was used to map the genetic defect in 23 RD families. The families were analyzed for homozygosity at the known arRP loci using highly informative microsatellite markers and were analyzed for homozygous chromosomal regions by genome-wide SNP microarrays. Known RD genes residing in homozygous regions were screened for mutations by sequence analysis. Identified mutations were analyzed in a cohort of 28 or 44 Pakistani RP probands and 100 ethnically matched control individuals by allele-specific PCR or restriction fragment length analysis. In the Pakistani families with RD that were studied, the occurrence of autosomal recessive, autosomal dominant and X-linked inheritance forms was found to be 87%, 6%, and 2% respectively while 3% families were with uncertain genetic mode of inheritance. We thus conclude that autosomal recessive forms of the disease are more frequent among RD patients in the Pakistani population compared to other populations of the world. Homozygosity mapping and candidate gene analysis resulted in the identification of seven novel mutations, including four in known arRP genes; one in CRB1, one in PDE6B, two in CNGB1 while one known mutation was identified in RHO. In addition one novel mutation was identified in GRKI causing Oguchi disease, two novel mutations, one in CNGA3 and CNGB3 were identified in patients suffering from achromatopsia. In addition to these novel mutations, a new arRP locus at chromosome 11 was identified in a large consanguineous family. The 7 iifamilies that excluded known arRP loci showed homozygosity at different chromosomal locations that needs to be further confirmed through microsatellite markers. The current genetic studies of RD was helpful in obtaining the correct diagnoses of RD families who had previously been clinically misdiagnosed and facilitated the provision of a clinical therapy for patients of achromatopsia. In addition genetic counseling was carried out in those areas of Pakistan where there is little awareness of inherited diseases.