تاویل نصوص کی شرعی حیثیت

The two fundamental sources of Islam are the Qur’an and Sunnah (Life) of the Hope Prophet (peace be upon him). Rulings and Legal interpretation are based in light of these two sources, and these two sources are used to determine the correct way of living. Some rulings are clear cut and explicit without any need for interpretation, while other rulings are not so clear cut and are very vague and open to multiple interpretations. Sometimes, in order to understand these vague rulings, there is a need to use different construed methods of interpretations, so that these commandments can become easier to understand and explain. The meaning of construed here is to use those interpretations which is not used commonly in order to explain the verse of life style of the beloved messenger. However, this is not something that any average human being can do, rather one must be a scholar of the highest caliber and have expertise in the field of interpretation. Additionally, the construed interpretation must be valid according to the principles of interpretation, and must have been used before in a previous interpretation. One other thing to note here is that there are many different types of taweel i.e construed interpretations. Some are correct while others are incorrect. This is why it is important to know and understand the correct use of construing and non-construing interpretations in the field of Islamic jurisprudence, so that one can differentiate between the two. Another tragedy of today is that every person thinks that they should and do have the ability to interpret the Qu’ran and the Sunnah on their own, and without any expertise in interpretation, come up with and begin to interpret the Qur’an on their own. This results in wrong interpretations, which not only misguides the individual, but countless others as well. This is a fact that the many different sects in Islam considered deviant by the majority, they all have begun with incorrect and deviant understandings and interpretations on the sacred texts in Islam.

Molecular Genetic Analysis of Autosomal Recessive Primary Microcephaly and Eye Disorders in Pakistani Kindreds

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.