This study was conducted to identify the loci and genes responsible to cause congenital neurological inherited diseases in selective Pashtoon families of Khyber Pakhtunkhwa region of Pakistan. For this purpose, five consanguineous/tribal endogamy families (A-E) suffering from oculocutaneous albinism, usher syndrome, primary microcephaly, and isolated clinical anophthalmia were selected and pedigrees were drawn. Blood samples were collected with informed consent from affected, as well as normal members of these families, and screened for disease associated mutations. These families were analyzed for linkage to all the known loci of oculocutaneous albinism, usher syndrome, primary microcephaly, and isolated clinical anophthalmia, using microsatellite STR markers. Direct sequencing was performed to find out disease associated mutations in the candidate genes. Molecular genetic analysis of family A with oculocutaneous albinism and golden red hair at birth was mapped to MC1R locus on chromosome 16q24.1. A novel mutation c.917G>A of MC1R gene was found to be consisting with OCA2 phenotype in family A. The identification of c.917G>A mutation in Pakistani family and its direct association with OCA2 phenotype is the first demonstration of a mutation of MC1R gene responsible for causing OCA2 phenotype in humans. By genetic linkage analysis, family B with diseased phenotype of Usher syndrome was mapped to USH1F locus on chromosome 10q21.22 (USH1F), which harbors PCDH15 gene. On sequencing of the PCDH15 gene, a novel homozygous c.1304 A>C transversion mutation was identified to be associated with the usher phenotype in the USH1F mapped family. This c.1304 A>C mutation predicts an amino-acid substitution of aspartic acid with an alanine at codon 435 (p.D435A) of PCDH15 protein product.Two families C and D with primary microcephaly were mapped to ASPM gene locus. On mutation screening of ASPM gene by PCR amplification and direct DNA sequencing, a common c.3978G>A transition, was identified in exon 17 of ASPM gene to be responsible for diseased phenotype in both the families. The identified mutation results into the substitution of an amino acid residue at position 1326 from tryptophan to a stop codon (i.e., p.Trp1326Stop). The family E with isolated clinical anophthalmia was mapped to SOX2 gene, which is located at chromosome 3q26.3-q27. On exonic and regulatory regions mutation screening of SOX2 gene, no disease-associated mutation was identified. It shows that another gene responsible for the development of eye might be present at chromosome 3q26.3-q27 and need to be identified and screened for disease- associated mutation in this family. It was concluded that the disease phenotypes of families with oculocutaneous albinism, usher syndrome, primary microcephaly, and isolated clinical anophthalmia were mapped by genetic linkage analysis. The candidate genes (MC1R, PCDH15, ASPM and SOX2) in the mapped regions were screened for disease associated mutations by PCR amplification and direct DNA sequencing. The novel disease- associated mutations were identified in MC1R and PCDH15. The disease associated mutation identified in ASPM gene was also reported in several other families of Pakistani origin with primary microcephaly. However, no disease associated mutation was identified in SOX2 gene, which indicates that possibly another gene might be present in the mapped region for disease phenotype.
It is well fact that before the advent ofthe Prophet Mu hammad (PBUH) the whole world was in totally darkness. Oppression was the order of the day. Womenfolkwas the most depressed segment ofthe society but when Islam cameit notonlyenjoined it followers to strive for theestablishmentofa just society in all walks of life. The issues of oppression of women folk was particularly addressed. Many verses ofthe Holy Quran and Sunnah clearly elaborated the duties as well rights of women. Islam considers woman as equal to man in respect ofduties and rights keeping her physical difference in view. In this article six points have been chosen for discussion which are as under equality of woman with man in humanity, equality in rights and obligation, equality in ownership and employment, equality in responsibility and equality in punishments Equality in liaan process.
The current study has been designed to detect multiple anthelmintic resistance against gastrointestinal nematodes in small ruminants reared at central and northern Punjab, Pakistan. The potential production of small ruminants is greatly affected by the development of anthelmintic resistance. The rates of appearance of anthelmintic resistance against gastrointestinal nematodes all over the world appear to differ geographically and in accord with the current climate, parasites type and treatment regime adopt in the region. Various in vivo and in vitro methods were used to detect multiple anthelmintic drugs resistance. First of all, to conduct a comprehensive studies on selected sheep and goat herds to evaluate the reliability of treatment with wide spectrum anthelmintic drugs using faecal egg count reduction test (FECRT) and, concurrently, to undertake in vitro egg hatch assays (EHA) to evaluate the susceptibility of nematode to anthelmintic drugs. Mean faecal egg count, percentage reduction and 95 per cent confidence interval were calculated by using the formula recommended by the World Association for the Advancement of Veterinary Parasitology (WAAVP) for detecting multiple anthelmintic resistant gastrointestinal nematodes of ruminants. Multiple anthelmintic resistance was found in selected goats and sheep flocks. All flocks were found resistance against the albendazol; six were resistance against levamisol, two suspected for resistance. Seven flocks were susceptible against Ivermectin while one is suspected for resistance. The results revealed that a significant difference (P<0.05) of FECRT were found on pretreatment and after post-treatment with different anthelmintic drug as compared to control group in all the flocks. The results against albendazol were also confirmed by the Egg Hatch Assay (EHA). Results of EHT revealed that all the eight flocks found positive for resistance against albendazol. The LC50 values ranged from 0.138 μg/mL to 0.152 μg/mL, which confirmed the results of FECRT.