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Genetic Analysis of Human Hereditary Nail Dysplasia in Pakistani Families

Thesis Info

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Author

Khan, Anwar Kamal

Program

PhD

Institute

Kohat University of Science and Technology

City

Kohat

Province

KPK

Country

Pakistan

Thesis Completing Year

2019

Thesis Completion Status

Completed

Subject

Biotechnology

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/12270/1/Anwar%20kamal%20khan%20biotechnology%202019%20Kust%20kohat%20prr.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676726271241

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In human, genetic disorders of the nails are very rare and occur in both isolated and syndromic form. In syndromic forms, anomalies in other ectodermal appendages and/or skeletal deformities are associated with nail disorders. Over the past few years several, different types of human nail disorders have been characterized at clinical and molecular levels. In few cases of nail disorders, causative genes have been identified. In the study presented in the dissertation, eight Pakistani families (A-H) representing isolated form of nail dysplasia (Families A-F) and syndromic nail disorders (Families G and H) have been characterized both at clinical and molecular levels. Family A showed autosomal recessive isolated congenital fingernail dysplasia. Whole exome sequencing of the family revealed a novel variant c.92G>T (p.Arg31Leu; MAF=0.0001; chr10:70,287,041) in the SLC25A16 (NM__152707.4) gene. Affected individuals in two families, B and C, showed typical phenotypes of hereditary leukonychia. Based on the phenotypes observed the PLCD1 gene was sequenced in all available individuals of both families. Analysis of sequencing data showed a recurrent heterozygous mutation c.625T>C (p.Cys209Arg; MAF=0.00009; chr3: 38,052,933) in family B. In family C analysis of sequencing data did not reveal any mutation in PLCD1 (NM_001130964.1) gene. To ascertain the causative gene, the DNA sample of an affected family member has been submitted for exome sequencing. In two other families (D and E) of isolated nail dysplasia, linkage was established to mapped on chromosome 8q22.3. Subsequent sequencing of the FZD6 (NM_003506.4) gene revealed a homozygous non-sense variant c.1750G>T (p.E584X*; MAF=0.00001; chr8:104,342,091) in family D and a homozygous missense variant c.1266G>A ( p.Gly422Asp; MAF=0.00001; chr8:104,342,091) in family E. In family F the nails of Genetic Analysis of Human Hereditary Nail Dysplasia in Pakistani Families the affected individuals were thick and hard with deformed nail bed. After failing to establish linkage to the known genes in the family, DNA samples were used for SNP microarray genotyping. This identified four homozygous regions. To identify a causative gene in the linked regions, DNA sample of an affected individual has been submitted to exome sequencing. In family G, affected individuals displayed typical phenotypes of pure hair and nail ectodermal dysplasia. All affected individuals of the family showed homozygosity with several markers related to HOXC13 (NM_017410.3) gene at chromosome 12p11.1- q21.1. Sequence analysis of HOXC13 revealed a novel homozygous missense mutation c.929A>C (p.Asn310Thr; chr12: 54,338,976). Family H segregated autosomal recessive form of primary hypertrophic osteoarthropathy. Homozygosity mapping, based on whole genome SNP genotyping, lead to the identification of 7.05 Mb homozygous region at chromosome 4q34.1-q34.3. The HPGD (NM_000860.6) gene, located in the homozygous region, was sequenced which detected a homozygous missense variant c.577T>C (p.S193P; chr4: 175,414,387) in all affected family members. The study presented here involves the clinical and genetic analysis of eight families collected from different remote areas of Pakistan. Six of them were characterized by isolated congenital nail dysplasia while two others with syndromic nail disorders. In these families mutation analysis of SLC25A16, PLCD1, FZD6, HOXC13 and HPGD genes revealed some novel and recurrent mutations. In addition, failure to establish linkage to known genes in two families (C and F) directed the existence of undiscovered genes in the human genome triggering nail dysplasia phenotypes.
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ندیم صادق کا پہلا شعری مجموعہ

ندیم صادق کا پہلا شعری مجموعہ
میں ندیم صادق صاحب سے حال ہی میں متعارف ہوا ہوں۔مجھے ان کے پہلے مجموعہ کلام کا مسودہ دیکھنے کا موقع ملا ہے۔ یہ میرے لیے ایک بہت خوش گوارتجربہ تھا۔ میرے لیے دل چسپی کی خاص بات یہ ہے کہ حصہ غزل کی تمام غزلیںناصر کاظمی کی’’ پہلی بارش‘‘کی طرح ایک ہی زمین میں ہیں۔ ان کی بحر بھی وہی ہے اور قافیہ بھی، ردیف البتہ مختلف ہے۔ شاعر نے کئی اشعار میں بھی ناصر سے اپنے لگائو کا اظہار کیا ہے۔ یہ کلاسیکی روایت سے متاثر اور وابستہ شاعر کا کلام ہے۔ کتاب کا عنوان میر کے شعر سے اخذ کیا گیا ہے اور انتساب ناصر کاظمی کے نام ہے۔
ایک ہی زمین میں اتنی غزلیں کہہ لیناکوئی آسان کام نہیں۔شاعر اس کے لیے خصوصی داد کا مستحق ہے۔ پہلی غزل حمدیہ ہے اس کے بعد اکیس غزلیں دو انسانوں کے ملنے بچھڑنے اور ان کے تعلق کے مختلف پہلوئوں کا بیان ہیں۔ چند اشعار دیکھیے:
یاد کے بوٹے سوکھ نہ جائیں
دل دریا پانی دیتا ہے

وہ تجھ کو کیوں یاد کرے گا
صادق وہ مصروف بڑا ہے

ساری گلیاں گھوم چکا ہوں
تیری گلی سے ڈر لگتا ہے

شہر کی سڑکیں تو ٹھنڈی ہیں
لیکن میرا دل جلتا ہے

دل میں کیسا خوف بھرا ہے
پھول کھلے تو ڈر لگتا ہے

اب دل تنہا خوش رہتا ہے
میں نے خود کو بدل لیا ہے

صادق فون نہ کر تُو اس کو
وہ تجھ سے بیزار ہوا ہے
میں ندیم صادق کو اس مجموعے کی اشاعت پرتہ دل سے مبارک باد دیتا ہوں اس دعا کے ساتھ یہ قارئین میںپذیرائی حاصل کرے۔
باصر سلطان کاظمی

A Study of Stress Factors and Their Impact on Students’ Academic Performance at University Level

The main emphasis of the study is on the academic performance and the stress management in applied science among the students of Mohtarma Benazir Bhutto Shaheed Sindh University Campus Dadu. What is the level of stress on the academic success of the students? How does it affect their lifestyle and health? This is what the research study covers to counteract the general stress among the students. The purpose of the study is to inquire and bring light to measure and check the present stress among students of the university. While doing the research a quantitative method was applied for collecting and analyzing the data. The Questionnaires were distributed among different students for this purpose. Innumerable factors of stress were found in the results and the factors were grouped in four categories which are; -Environmental Factors, Academic Factors, and Personal Factors. In environmental factors, the stress was about the happening the fate in the future. The students were found worried about future that what would happen about their fate? How it will happen? What is about to happen? When they came into contact with the new people it raised their stress. Also the class workload was the main reason for the stress among the students regarding academic factors. When the students were experiencing the workload of the class the group of the students came under stress. The last factor was a personal factor which was mainly due to the financial problem among the students. The stress of all categories can be managed through stress management courses and doing different extracurricular activities which will help to divert the attention of the students on different occasions. This study has drawn significant conclusions and Suggests further measures for practitioners which could help other to manage stress. The limitations are also mentioned so that those who are conducting research for the similar cases can extract better results and ways of curbing stress. A survey questionnaire was designed to collect the response from students, the five-point Likert scale was used from strongly agree to strongly disagree. SPSS-21 version was used to interpret the results through different quantitative techniques like descriptive, regression, and correlation. ____________

Boron Dynamics in Alkaline Calcareous Soils and its Availability under Wheat-Cotton Cropping System

Wheat (Triticum aestivum L.) is the world’s leading cereal crop and is unanimously consumed as staple food product of almost hundred percent Pakistani nationals as well as about 1/3 rd population of the world. Cotton (Gossypium hirsutum L.) is an important cash crop of Pakistan but the yields of wheat and cotton in Pakistan have been stagnated throughout the preceding decade due to improper fertilizer management and non- exploitation of micronutrients specially boron. Boron (B) is extraordinary amongst the microelements in that an extremely diminutive amount is required for ordinary growth and maturity of plants, and simply somewhat greater B concentrations are toxic. A three- year (2005-2008) study was initiated to determine the boron status of soils under wheat- cotton system and also to assess the relationship between soil B and physico-chemical properties of soils. B content present in canal and tubewell waters being used by wheat- cotton, were also assessed. The responses of cotton and wheat crops to foliar and soil applied B were also studied under field conditions. Almost all the soils were calcareous in nature (92 % area), alkaline in reaction (83 % area had pH > 8) and 100 % area had OM < 1 %. In case of soil B content, 82 % soils were deficient in B (0.10 to 0.45 μg g -1 ), 15 % were adequate (0.46 to 0.55 μg g -1 ) and only three samples were sufficient (0.56- 0.91 μg g -1 ). More B was observed in the fine textured soils (28 % area). Low B concentrations were observed in wheat and cotton plants. The average B concentrations during 2006 and 2007 in wheat leaves were 8.86 and 4.41 mg kg -1 , and in cotton 37.78 and 15.83 mg kg -1 . Mean B content in canal water was more during monsoon season (0.14±0.10 mg L -1 ) as compared to that during winter season (20±0.13 mg L -1 ), respectively. Whereas, B concentration was more in tubewell waters as compared to that in canal waters. B fractionation study revealed that the highest mean plant available B (0.32±0.12 mg kg -1 ) was obtained by hot water extraction followed by 0.05M HCl (0.31±0.12 mg kg -1 ), and 1:2 water extraction whereas the lowest B concentration was extracted by 0.005M DTPA. Total soil B content of all the soils varied from 15.61 to 152.80 mg kg -1 and it was further fractionated by using 0.05 M HCl (readily soluble B), 0.05 M KH 2 PO 4 (exchangeable B), 0.02 M HNO 3 -H 2 O 2 (extractable B), 0.25 M NH 4 - oxalate extractable B and the residual B. The highest mean B fraction was the residual fraction (70.50 mg kg -1 ) whereas the lowest was the water soluble B (0.33 mg kg -1 ). Field 15experiments were conducted at three different textured soils (loam, sandy clay loam and silt loam). Ten B treatments were applied to soil (0.00, 0.25, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00 and 3.00 kg B ha -1 at sowing along with recommended NPK fertilizers for -1 cotton and wheat. Whereas five B levels (0.00, 0.25, 0.50, 0.75 and 1.00 kg ha ) were used for foliar application in three replications in RCBD, while all other recommended nutrients for cotton and wheat were applied. Foliar sprays were performed on cotton before flowering, at flowering and at boll formation stages while on wheat before tillering, at booting and at milking stages. B application as soil and foliar sprays significantly increased the number of bolls, boll weight, lint, seed cotton, dry matter yield, lint percent, leaf B concentration and total B uptake. Foliar use of B (0.50 kg B ha - 1 ) increased the seed cotton yield by 25.60 % over control on loamy soil followed by that on silt loam soil (23.80 %), however during the next year (2007), seed cotton yield mildly decreased compared to first year at the same B application level of 0.50 kg B ha -1 but it remained significantly higher than control by 8 and 21.50 % at loam and silt loam soil (23.80 %), respectively. Likewise, wheat crop significantly responded to B application both as soil and foliar in terms of grain and straw yields, number of grains spike -1 , 1000- grain weight, plant height, plant B concentration and total B uptake while it had non- significant effects on tillering and protein content. B application improved the grain yield by around 6, 9.60 and 6 % at B application levels of 0.50, 0.75 and 1 kg ha -1 , respectively. Finally, the residual or carry-over study revealed significant responses of wheat crop to residual B applied to previous cotton crop. Residual B significantly improved the grain and straw yields, number of grains spike -1 , 1000-grain weight, plant height, plant B concentration and total B uptake and protein content of wheat. The highest and the lowest protein content of 14.54 and 11.17 % were obtained with residual B levels of 1.50 and 3 kg ha -1 , respectively.