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Molecular Markers of Susceptibility to Prion Diseases in Local Humans and Domesticated Bovids

Thesis Info

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Author

Imran, Muhammad

Program

PhD

Institute

University of Health Sciences

City

Lahore

Province

Punjab

Country

Pakistan

Thesis Completing Year

2012

Thesis Completion Status

Completed

Subject

Biology

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/11142/1/Muhammad%20Imran_Cellular%20%26%20Molecular%20Biology_2012_UHS_PRR.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676726712442

Similar


This thesis presents the lacking information on genetic susceptibility of Pakistani population to human prion disease variants and of local domesticated bovids to Bovine Spongiform Encephalopathy (BSE). In study 1, a total of 909 unrelated individuals including 221 hemophiliacs representing all 4 major provinces of Pakistan were screened for M129V polymorphism and insertions or deletions of octapeptide repeats (OPRIs/OPRDs) using Polymerase Chain Reaction coupled with Restriction Fragment Length Polymorphism (PCR-RFLP). Concordance of the results of some PCR-RFLP reactions was also confirmed by dideoxy automated Sanger sequencing. The frequencies of M129V alleles (129M and 129V) and genotypes (129MM, 129MV and 129VV) were found in all 909 individuals to be 0.7101, 0.2899, 0.5270, 0.3663 and 0.1067, respectively. Deletion of 1 octapeptide repeat (1-OPRD) was detected in heterozygous state in PRNP of 10 individuals and in homozygous state in 1 individual. An insertion of 3 octapeptide repeats (3-OPRI) was found in 1 individual and an insertion of 1 octapeptide repeat (1-OPRI) in two individuals. Both 3-OPRI and 1-OPRI were present in heterozygous state and were linked to 129M allele. There were no significant χ2 differences between M129V allelic and genotypic frequencies of healthy individuals and hemophiliacs. However, M129V allelic and genotypic frequencies differed significantly between Pakistani population and East Asian and Western populations. Non-significant χ2 differences between M129V frequencies of healthy individuals and hemophiliacs suggest that individuals manifesting single gene disorders may provide naturally randomized samples for studies aiming at surveying the genetic variation. The combined excess of 129MM and 129VV homozygosity and the presence of 3-OPRI in 1 individual imply that Pakistani population may be susceptible to prion disorders. In study 2, a total of 236 cattle from 7 breeds and 281 buffaloes from 5 breeds were screened for E211K polymorphism and 23 bp and 12 bp indels employing triplex PCR. The E211K polymorphism was not detected in any of the animals studied. The 23 bp insertion allele was underrepresented in studied cattle breeds while the 12 bp insertion allele was overrepresented. Both 23 bp and 12 bp insertion alleles were overrepresented in studied buffalo breeds. Almost 90% of alleles were insertion alleles across all studied buffalo breeds. The average frequency of 23 bp and 12 bp insertion alleles across all studied cattle breeds was found to be 0.1822 and 0.9407, respectively. There were significant differences between Pakistani and worldwide cattle in terms of allele, genotype and haplotype frequencies of 23 bp and 12 bp indels. The higher observed frequency of 12 bp insertion allele suggests that Pakistani cattle are relatively more resistant to classical BSE than European cattle.
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سید حسین

سید حسین
دوسرا بڑا حادثہ مسٹر سیدحسین کی وفات ہے، مرحوم ہندوستان کی تحریک آزادی کے دور اول کی یادگار، انگریزی زبان کے بہترین خطیب و انشا پرداز اور نامور صحافی تھے، عرصہ تک الہ آباد کے مشہور پرانے اخبار انڈیپنڈنٹ کے اڈیٹر رہے، پھر وفد خلافت میں لندن گئے اور غالباً وہیں سے امریکہ چلے گئے اور پچیس تیس سال تک وہاں اپنے قلم و زبان سے ہندوستان کی خدمت کرتے رہے اور امریکہ کے سیاسی اور صحافتی حلقوں میں بڑا نام پیدا کیا، ہندوستان کی آزادی کے بعد وطن واپس آئے اور نومبر ۱۹۴۷؁ء میں حکومت ہند کی جانب سے مصر کے سفیر بناکر بھیجے گئے، اور وہیں گذشتہ فروری میں انتقال کیا، آئندہ مسلمانوں میں ایسے صاحب کمال مشکل سے پیدا ہوں گے، اﷲ تعالیٰ مرحوم کی مغفرت فرمائے، ان کی وفات پر ہندوستان کے اکابر کی خاموشی حیرت انگیز ہے۔
(شاہ معین الدین ندوی، مارچ ۱۹۴۹ء)

سیّد حسین کی موت
۲۵؍ فروری ۱۹۴۹؁ء کی رات کو ۹ بجے ریڈیو نے خبر سنائی کہ ہندوستانی سفیر متعین مصر سید حسین نے وفات پائی، دوسرے دن شاہانہ تزک و احتشام سے سرکاری طور سے ان کی تدفین عمل میں آئی، جنازہ میں شاہ فاروق نے شرکت کی اور بعض علمائے ازہر نے ان کی نماز جنازہ پڑھائی۔
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