ترے دعوے ،ترے وعدے کبھی سچے نہیں نکلے
کہ ہم تکتے رہے تھے راہ تم گھر سے نہیں نکلے
کہیں کیا، حادثہ تو روز ہی ہوتا رہا کوئی
یوں اچھے دن بھی اپنے خیر سے اچھے نہیں نکلے
یہی ہے عشق جب بھی پھونک ڈالا آگ نے گھر تو
کھلونے چھوڑ کر باہر کبھی بچے نہیں نکلے
دمِ آخر جو میرے ان لبوں پر نام تھا اُن کا
وفاؤں کے یہ دھاگے شکر ہے کچے نہیں نکلے
تری تو ہے خدائی اے خدا سارے جہانوں پر
تعجب ہے کہ تجھ سے بھی مگر رستے نہیں نکلے
Wherever person goes, he finds unless it finds advertisement tools in various shapes and sizes. These ads, which have become an important pattern in the life of traders are indispensable for them than in contemporary reality. But now companies are specializing in the production of these ads and incentives, taking advantage of all the modern means of magazines and broadcasting video and audio formats and even mobile internet services. Each of these companies have their own philosophy of it, some of which consider the legitimate controls in advertisements but other are to make money regardless of the appropriateness of these ads or following the controls of legitimacy and this research aims at highlighting the most important of these Islamic perspective controls which must be adhered when designing these commercials ads. Islam regulates the trade system and provides a sound guideline to its followers. It has forbidden all the malpractices being exercised in business and its advertisement. The research talks about the commercial advertisements, their types, aims and the opinions of Islamic experts about them. Besides, the research proves that advertisement is permissible according to shariah.
The main objective of the present investigation is to understand the molecular genetics of autosomal recessive genetic disorders in the Pakistani population by studying primary microcephaly and certain eye disorders i-e primary congenital aphakia, primary congenital glaucoma and retinitis pigmentosa. Autosomal recessive primary microcephaly (MCPH) is a neuro-developmental congenital disorder in which the affected individuals have significantly reduced brain size (occipitofrontal head circumference at least -4SD) accompanied with mild to moderate intellectual impairment. Though MCPH has a single clinical phenotype, it is a genetically heterogeneous disorder with seven loci reported to date (MCPH1 through MCPH7). Twenty MCPH families (designated as MCP) were ascertained from various regions of Pakistan. Linkage analysis was performed for all the families as a result of which five families established linkage to MCPH2, one family to MCPH4, eight families were found linked to MCPH5, two families to MCPH6, four families were found unlinked to any of the reported locus, one of which was later found linked to the seventh locus MCPH7. Since the underlying genes have not yet been identified for both MCPH2 and MCPH4, candidate gene approach was used to find the gene responsible. Six potential candidate genes (MAG, SIRT2, ZNF302, ZNF599, CHST8 and SNX26) were sequenced for MCPH2 linked families and nine genes (BUB1B, CHAC1, CHP, COPS2, FGF7, NUSAP1, PAK6, RHOV and TYRO3) were selected and sequenced for the MCPH4 locus, which did not reveal any pathogenic mutation. Since sequencing all the candidate genes for both these loci was beyond the scope of this study, the high-throughput sequencing facility was then used to sequence the candidate regions coupled with DNA capture experiments to capture only the regions of interest rather than sequencing the entire genome. XIIIEight families linked to MCPH5 which is the most common locus responsible for MCPH. Mutation screening of the underlying gene ASPM in these families revealed 4 novel and 3 known mutations. The novel mutations identified in the present study are, c.9677_9678insG, c.2938C>T, c.9595A>T and c.7894C>T, all leading to a premature stop codon. Four families linked to this locus shared three known mutations (c.8508_8509delGA, c.3978G>A and c.9730C>T) which have already been reported. Two families (MCP10 and MCP26) established linkage to MCPH6, whose gene is CENPJ. Extensive bi-directional sequencing of all the coding exons as well as exon- intron boundaries did not revealed any pathogenic mutation. Four MCPH families (MCP12, MCP23, MCP30 and MCP33) were initially found unlinked to any of the known loci, and subjected to homozygosity mapping by using SNP 6.0 array. Large homozygous regions were identified across the genome which will be further narrowed down to obtain the minimum critical regions. By the discovery of the seventh locus (MPCH7), MCP12 was found to have linkage to the MCPH7 locus with the underlying gene STIL. Bi-directional sequencing of all the coding exons of STIL has not revealed any mutation. Molecular genetic analyses of autosomal recessive eye disorders comprise the second part of this dissertation. Eye disorders could either present as isolated entity or combined with other phenotypes to have a syndromic manifestation. Inherited eye disorders are genetically heterogeneous as they have a wide range of phenotypic outcome. Family CT-1 was diagnosed to have primary congenital aphakia wih complete absence of lens. Initially, screening for all thirteen autosomal recessive cataract loci was done, to rule out surgical cataract removal, but the family was found linked to 1p34.3-p32.2 XIVharboring the gene FOXE3 which is responsible for causing aphakia. Sequence analysis revealed a nonsense mutation c.720C>A, changing cysteine 240 to a stop codon (p.Cys240X). The mutation was counter confirmed using a restriction enzyme DdeI. Since this mutation has already been reported in a family from Madagascar, haplotype analysis was done for both families which ruled out the ancestral origin of the mutation. Family RP5 had the clinical diagnosis of primary congenital glaucoma with secondary cataract. CYP1B1 is the candidate gene for this phenotype, whose sequence analysis revealed a novel frameshift mutation 862insdelG>CC (p.A288fsX326). This frameshift mutation leads to a premature stop codon truncation 38 amino acids downstream. Families RP6 and RP7, initially diagnosed as early-onset blindness, were subjected to SNP 6.0 array for homozygosity mapping to identify homozygous regions. Analysis of RP6 family is still underway. However in family RP7, by combining the SNP 6.0 data and marker analysis, a reported nonsense mutation (p.W278X) was found in the gene AIPL1, known to be responsible for causing Leber Congenital Amaurosis. The work presented in this thesis has been published in the following articles: 1. Aujum I, Eiberg H, Baig SM, Tommerup N, Hansen L (2010). A mutation in the FOXE3 gene causes congenital primary aphakia in an autosomal recessive consanguineous Pakistani family. Mol Vis 16:549-555. 2. Muhammad F, Mahmood Baig SM, Hansen L, Hussain MS, Anjum I, Aslam M, Qureshi JA, Toilat M, Kirst E, Wajid M, Nurnberg P, Eiberg H, Tommerup N, and Kjaer KW (2009). Compound heterozygous ASPM mutations in Pakistani MCPH families. Am J Med Genet A 149A (5): 926-30.