The study reported in this thesis document was undertaken to characterize molecular and genetic basis of primary congenital glaucoma (PCG) in Pakistani population. For this purpose, traditional strategy of homozygosity mapping was used to identify disease causing mutations and to map novel loci/genes responsible for autosomal recessive primary congenital glaucoma (arPCG). Thirty consanguineous families with arPCG were enrolled from different parts of Pakistan. Genomic DNAs from these families were subjected to linkage analysis for the exclusion of previously reported genes/loci for autosomal recessive primary congenital glaucoma. The phenotypes of 17 PCG families (PKGL028, 032, 040, 047, 050, 051, 058, 060, 065, 066, 067, 068, 069, 070, 071, 072 & 073) were found linked to GLC3A locus harboring Cytochrome P450 Family 1 Subfamily B Member 1 (CYP1B1) gene. Sanger sequencing of CYP1B1 identified five missense mutations; p.Y81N, p.E229K, p.R368H, p.R444Q and p.R469W in families PKGL051, PKGL047, PKGL058, PKGL050 and PKGL028 respectively. Another homozygous missense mutation; p.R390H was identified in nine PCG families designated as; PKGL040, PKGL060, PKGL065, PKGL066, PKGL067, PKGL069, PKGL070, PKGL071 and PKGL073. In PKGL032, a 10bp homozygous duplication; c.1200_1209dupTCATGCCACC (p.T404Sfs*30) was identified. Two novel frameshift mutations; p.W246Lfs*81 and p.P442Qfs*15 were identified in PKGL047 and PKGL068 respectively. Furthermore, mutational analysis identified a known homozygous nonsense mutation; p.Q37X in family PKGL072. Three consanguineous families; PKGL042 PKGL015 and PKGL076 were found linked to another known PCG locus; GLC3D harboring Latent Transforming Growth Factor Beta Binding Protein 2 (LTBP2) gene. Sanger sequencing of LTBP2 identified two missense and a frameshift mutation; p.D1010N, p.Q1143Rfs*35 and p.C1757Y in PKGL076, PKGL015 and PKGL042 respectively, all of these were novel. These results show that pathogenic mutations in CYP1B1 and LTBP2 gene are responsible for PCG phenotype in these nineteen families. Three large consanguineous PCG families which remained unlinked in linkage studies were selected for genome wide scan. A novel locus for autosomal recessive primary congenital glaucoma was mapped to chromosome 1p33-32.3 in one family; PKGL061 with a maximum two point LOD score of 5.33 obtained with marker D1S386 at recombination fraction zero. This study reports identification of five novel and eight known pathogenic mutations in already reported genes; CYP1B1 and LTBP2. Furthermore, a novel disease locus at chromosome 1p33-32.3 in a large consanguineous PCG family was identified. These findings provide insight into genetic and molecular determinants responsible for autosomal recessive primary congenital glaucoma, thus providing a better understanding of mechanisms underlying the disease.
جسٹس سیّد امیرعلی مرحوم سیدامیرعلی مرحوم تمام تر جدید تعلیم کی پیدوار تھے، مگر انہوں نے بزرگوں کے سُنے سُنائے معلومات اور ذاتی کدو کاوش سے یورپ میں اسلام کی بڑی خدمت کی، وہ یورپ میں تمام اسلامی کاموں اور تحریکوں کے رکن رکین سمجھے جاتے تھے ان کے مذہبی اور سیاسی خیالات سے گوہم موافقت نہ کرسکیں، مگر اس میں کوئی شبہ نہیں کہ ان کے قلم کی ضوافشانی سے اسلام کے متعلق یورپ کے بہت سے خیالات باطلہ کے بادل پھٹ گئے، ان کی دوکتابیں اسپرٹ آف اسلام اور ہسٹری آف ساراسینس ہمیشہ یادگار رہیں گی، ان دونوں کتابوں کے ترجمے اکثر اسلامی زبانوں میں موجود ہیں، حتیٰ کہ عربی میں بھی ہوچکے ہیں، ۷۹ سال کی عمر میں اس جہان فانی کو الوداع کہا، مرحوم سے ۱۹۲۰ء میں کئی دفعہ لندن میں ملنے کا موقعہ ملا تھا، رحمۃ اﷲ تعالیٰ۔ (سید سلیمان ندوی، اگست ۱۹۲۸ء)
Orientalists contributed much regarding their study of the Holy Qur’ān, Hadith and Sīrah since eighteenth century. Few of them attracted Muslim scholars due to the quality of their work about Islam, like the translation of the Holy Qur’ān, the indexes of Hadith literature and the translations of Arabic Sīrah books in English. These orientalists have left a positive impression regarding their contributions in introducing Islamic literature in West in their native languages. This research paper aims to present the expression of religious positivity in modern orientalist Karen Armstrong’s Sīrah work. This selection is based on the status of this Sīrah writer in present time. Her books are best sellers written on comparative religion and a huge number of people study her books and appreciate her for expressing the positive image of Islam in West. In this study, it will be found out that in which style and angle she has presented her works regarding religious positivity especially the presentation of the personality of the Holy Prophet (peace be on him) to the non-Muslims and non-religious societies.
Let G = (V (G);E(G)) be a connected graph. The distance between two vertices u; v 2 V (G) is the length of shortest path between them and is denoted by d(u; v). A vertex x is said to resolve a pair of vertices u; v 2 V (G) if d(u; x) 6= d(v; x). For an ordered subset, B = fb1; b2; : : : ; bng of vertices of G, the n-tuple r(vjB) = (d(v; b1); d(v; b2); : : : ; d(v; bn)) is called representation of vertex v with respect to B or vector of metric coordinates of v with respect to B. The set B is called a resolving set of G if r(ujB) 6= r(vjB) for every pair of vertices u; v 2 V (G), i.e., the representation of each vertex with respect to B is unique. The resolving set with minimum cardinality is called metric basis of G. This minimum cardinality is called metric dimension and is denoted by _(G). Notice that the i-th coordinate in r(vjB) is 0 if and only if v = bi. Thus in order to show that B is a resolving set of G, it su_ces to verify that r(ujB) 6= r(vjB) for every pair of distinct vertices u; v 2 V (G) n B. Let G be a graph of order at least 2. Two vertices x; y 2 V (G) are said to doubly resolve the vertices u; v of G if d(u; x) ? d(u; y) 6= d(v; x) ? d(v; y): A subset D _ V (G) is called a doubly resolving set of G if every two distinct vertices of G are doubly resolved by some two vertices in D, i.e., all coordinates of the vector r(ujD)?r(vjD) can not be same for every pair of distinct vertices u; v 2 V (G). The minimal doubly resolving set problem is to _nd a doubly resolving set of G with the minimum cardinality. The cardinality of minimal doubly resolving set of G is denoted by(G). We have _(G) _(G) always. Therefore these sets can contribute in finding upper bounds on the metric dimension of graphs. In this thesis, we have investigated the minimal doubly resolving set problem for necklace graph, circulant graph, antiprism graph and M obius ladders. Also, in last part of thesis, the metric dimension problem has been investigated for kayak paddle graph and cycles with chord.