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Analysis of Human Genetic Variations in Pakistani Population

Thesis Info

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Author

Chishti, Hafsah Muhammad

Program

PhD

Institute

Quaid-I-Azam University

City

Islamabad

Province

Islamabad.

Country

Pakistan

Thesis Completing Year

2016

Thesis Completion Status

Completed

Subject

Biochemistry

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/14481/1/Hafsa%20M.%20Chisti_Biochem_2016_QAU.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676725484584

Similar


The diverse and complex/heterogeneous Pakistani population is categorized into more than 18 ethnic groups. A properly reported forensic DNA database for this seventh largest population of the world is still not available. This study contributes towards the development of a forensic DNA database of the Pakistani population comprising both autosomal short tandem repeat (STR) markers profiles and mitochondrial DNA (mtDNA) hyper-variable regions (HVRs) haplotypes. The obtained genetic data was used for phylogenetic and demographic analyses to study the structure of the Pakistani population. Additionally, the molecular diagnostic potential of the autosomal STRs was also evaluated for the detection of chromosomal aneuploidic conditions. DNA samples from 701 individuals belonging to the Punjabi, Pathan, Sindhi, Balochi and Hazara ethnic groups of Pakistan, were analyzed for fifteen short tandem repeat (STR) markers (TPOX, D2S1338, D3S1358, FGA, CSF1PO, D5S818, D7S820, D8S1179, THO1, VWA, D13S317, D16S539, D18S51, D19S433 and D21S11) included in the AmpFlSTR® Identifiler™ PCR amplification kit. Our data showed that four markers, D2S1338, D18S51, D19S433 and FGA exhibit high power of discrimination, while TPOX was the least discriminative among all studied loci. Subsequent analyses also revealed highly significant deviations from Hardy–Weinberg equilibrium at several loci in all the studied ethnic groups, which probably occurs due to frequently practiced inbreeding (consanguineous marriages) within each group. Further analyses with the clustering algorithm STRUCTURE, principal component analysis (PCA) and neighbour joining (NJ) tree did not show clear genetic differences among the five ethnic groups. However, differences were evident with Hazara ethnic group (emerged as a genetic out-group) when the analyses were performed by using the data of 783 microsatellite markers from the HGDP-CEPH panel. Most of the STR markers in the Identifiler kit are valuable forensic tools but they are insufficient for elucidating the population structure or capturing the demarcation and variation among the studied ethnic groups of Pakistan. As the STR genotype frequency data from these five studied ethnic groups did not show any remarkable differences, it is not possible to assign ethnicity to an unknown DNA sample belonging to any of these ethnic groups on the basis of the data derived from 15 STRs. This study also attempts to investigate the applicability of AmpFlSTR® Identifiler™ PCR amplification kit for quick and simultaneous diagnosis and tracing of parental source of common chromosomal aneuploidies. Samples from 74 patients with different aneuploidic conditions were evaluated for diagnostic strengths of these STR markers. Among these aneuploidic samples, 100% of the samples with autosomal trisomies were precisely detectable using Identifiler STRs, although aneuploidies involving sex chromosomes were not detectable. Parental origin of aneuploidy was traceable in 92.54% patients with autosomal trisomies, a finding that validated the diagnostic potential of 15 STR markers for the common trisomic conditions. In order to investigate mtDNA HVRs sequence variations, we evaluated the forensic potential of the three HVRs for applicability in the Pakistani population, especially in situations where nuclear DNA is degraded. For this purpose, sequence data were generated for 104 individuals belonging to the Punjabi, Pathan, Sindhi, Balochi and Hazara ethnic groups of Pakistan. The phylogenetic analysis and comparison of the sequence data indicated that the genetic diversity is 0.9901. A total of 184 polymorphic sites were observed among all samples in the HVR-I, HVR-II, HVR-III and some other part of the mtDNA. Later haplotype analysis showed the presence of 102 haplotypes. Interestingly, 100 haplotypoes were unique to a sample and thus present a high power of discrimination (99.76%) and can be promising for forensic applications in Pakistan. However the phylogenetic analyses of the mtDNA data could not yield the genetic structure of the Pakistani population. However, the screening of intergenic COII / tRNALys 9-bp deletion/insertion polymorphism in 1233 individuals from the above mentioned five ethnic groups as well as six additional ethnic groups of Pakistan (including Brahui, Burusho, Kalash, Balti, Makrani and Parsi) demonstrated Pathans as a highly heterogeneous bearing high percentages of previously called “Asia specific” 9-bp deletion (19%) and the so called European 9-bp insertion (3.8%). Overall, the 9-bp deletion was observed in 94.16% and 9-bp insertion in 0.9% samples in all of the 1233 studied samples. These data can establish more conclusive results in conjugation with the HVRs sequence data along with their global haplotype information to provide insights into phylogenetic history and genetic demographic structure of the Pakistani population. Overall this study has contributed towards the development of an ethnically categorized allele frequency database for the Pakistani population covering both the autosomal and mitochondrial DNA. In addition, Identifiler multiplex system is presented as a valuable approach for detection of many autosomal trisomic conditions.
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مل گئی یک مشت ان کو راحتِ دنیا و دیں


مل گئی یک مُشت اُن کو راحتِ دنیا و دیں
جن کی قسمت میں مدینے کی فضائیں ہو گئیں

نورِ ’’اقرا‘‘ کی ضیائیں ساتھ ساتھ آنے لگیں
جلوتوں میں آگئے جب غار کے خلوت نشیںؐ

صبحِ طیبہ میں بسی ایمان کی تابندگی
شامِ طیبہ میں نہاں ہے راحتِ قلبِ حزیں

بندگانِ ربِّ کعبہ کی یہی ہے بندگی
جس جگہ پہ نقشِ پائے مصطفی ہو خم جبیں

آسمانِ معرفت کی اُس کو رفعت مل گئی
مل گئی جس شخص کو طیبہ میں بس دو گز زمیں

بربطِ تخلیق کی آوازِ ہست و بود میں
خلقتِ نورِ محمدﷺ ہے صدائے اوّلیں

آپؐ کے دم سے جہانِ آب و گل میں تازگی
چہرئہ ارض و سما ہے آپؐ کے دم سے حسیں

خوبیٔ رفتار سے آگے مقامِ مصطفیؐ
وسعتِ پرواز کی حد سدرہ سے آگے کہیں

والہانہ اہلِ الفت کی نگاہوں نے کہا
چودھویں کے چاند سے ہے آپؐ کا چہرہ حسیں

مدحتِ ممدوحِ ربؐ کی وسعتوں کے سامنے
لفظ کے دامن میں تنگی کے سوا کچھ بھی نہیں

ہیں امامِ انبیاؐ ، اقصیٰ کی شب ، بدرالدجیٰ
مقتدی ہے ماہِ کنعاںؑ کی ادائے دل نشیں

شافعِ محشرؐ کے ابرو کا اشارا ہو گیا
مل گئی اُنؐ کی شفاعت سے ہمیں خلدِ بریں

کس طرح اُن کو ہو عرفانِؔ خدائے لم یزل
جن کو محبوبِ خداؐ کی ذات سے اُلفت نہیں

Developing An Improved Heart Rate Monitor With Work-Out Training Android Application And Real Time Audio Coaching

TechnoHeart is a digital way of monitoring heart rate using a Heart Rate Monitor device and an android phone. Moreover, this is made more special through its work-out training which is designed to help users set and achieve their target heart rate and monitor at what training intensity they are during a strenuous exercise. The training is made more interactive as the application has its real-time audio coaching. The need for this application comes from three sources; First, some athletes, non-athletes and even doctors are still using the traditional way of getting the heart rate; Second, training intensity is not monitored and target heart rate is not achieved; Third, most mobile developments do not tailor the need of users who undergo work-out training. With the following needs, objectives were set; First, to connect an HRM (Heart Rate Monitoring) device to an android mobile device and display individual’s heart rate in digital form through mobile; Second, to create a work-out training program using the Karvonen Formula; Third, to enable users know one’s target heart rate by using a Karvonen calculator; Fourth, to notify users in real time with every sudden change and the needed action in order to keep an effective training exercise. The project is to explore this and other similar concepts to develop a design that optimally satisfies all of these objectives. The project addresses all of these objectives while meeting the constraints given. The project was deployed in three different sets of users: The University of Mindanao Athletes, The elderly users aging from 50-80 years old and the other users aging from 12-49 years old. The researchers recommend the use of TechnoHeart for athletes and non-athletes who are aiming for an effective cardiovascular training. And for the next researchers, they can focus on the compatibility of the said application to other mobile platforms like iOS, Blackberry, Windows and etc. And also, they may upload application in the internet such as in social networking sites or any features that would make this project more usable.

Extending the Authentication Mechanism in Ip Multimedia Subsystems for Universal Mobile Telecommunication System

IP multimedia subsystem (IMS) is an emerging platform for provisioning multimedia services (e.g., data, voice, and video) in 4G/5G networks. IMS authentication is an important procedure which grants legitimate users to access multimedia services. However, periodic re-authentication of mobile users results in significant signaling traffic overhead due to complete execution of hectic procedure. Moreover, signaling protocol such as SIP overlooks user’s confidentiality by leaving unprotected public and private identities. In IMS each user entering from another network like UMTS or VOLTE has to authenticate itself. However, it already passed through the same authentication process in its own network. Therefore, IMS core entities are affected by high signaling that could be a source of congestion. . The Session Initiation Protocol (SIP) is used in IMS to establish and manage sessions. It is easy for a hacker to attack IMS with flooding SIP messages. However, IMS does not provide any functions to prevent such kind of attacks. This research presents a secure aauthentication protocol (SAP) which creates a secure channel through the deployment of KMC (Key Management Center) for transmitting user identities; ECC (Elliptic curve cryptography) is used for key generation that provides reduced encryption and decryption time than existing schemes for IMS. FAP strives to minimize signaling overhead of periodic re-authentications. Once a user completes authentication, FAP grants a valid ticket for a particular time which can be used for subsequent re-authentications until it expires. This research introduce a header in SIP to hold the ticket. This research employ protocol composition logic for formal modeling and verification of SAP. The performance of SAP, FAP is validated through FOKUS IMS test bed. The results demonstrate the performance appraisal of FAP compared to other contemporary schemes in terms of signaling overhead, bandwidth consumption and response time. This research presents a Low congestion and Certificate based One-pass Authentication Protocol (COAP) that avoids duplication of authentication steps and makes its authentication efficient through the use of digital certificates. An authenticated user is allotted a certificate to restrict the repetition of complete authentication procedure until the certificate expires. COAP results in reduction of signaling traffic, which eliminates v the congestion problem, it also reduces bandwidth and delivery cost which make this scheme more efficient in terms of bandwidth consumption. An intrusion detection system is designed where a pair of subsystems is working, one is spoofing detection and prevention subsystem and other is flooding detection and prevention subsystem. A zero-watermarking scheme detects the spoofing attack.Watermark embedding is done by the original author and extraction done later by KMC to prove ownership. The flooding detection system is working on misuse rules and anomaly detection algorithms which provide successful detection and prevention for IMS and VOLTE environment. The results has shown that better than other schemes it is compared to i.e. when the no of requests are 30 the detection rate is 90.19 however, when no of request are 40 the accuracy rate of the proposed scheme is 100 percent.