Factors Affecting Human Rights in Khyber Pakhtunkhwa, Pakistan

In Khyber Pakhtunkhwa the situation of human rights is comparatively worse. Factors affecting human rights in this province include failure to guarantee good governance, growing poverty, illiteracy, violence, terrorism, worsening security, social injustice, political instability, and economic turmoil. These factors have been affecting adversely the human rights. To ensure human rights in the province, the execution of international human rights laws needs to be implemented. It is required to ensure good governance, peace and stability to ensure viable environment, provision of sustainable and quality education and reduce poverty. Unless the favourable environment be provided to the people at large, human rights violations may be continued. This paper attempts to know about the factors affecting human rights in the province and present some solid recommendations and policy options.

Mapping of Genes Involved in Human Hereditary Infertility

Introduction: The World Health Organization defines infertility as the failure of achieving conception after one year of unprotected intercourse. Worldwide, approximately 15% of couples are affected by infertility and genetic anomalies account for 15-30% of male factor infertility. Nearly 15% of infertile males suffer from azoospermia in the form of obstructive azoospermia or non-obstructive spermatogenic failure. Polycystic Ovary Syndrome (PCOS) was contributing 6-10% infertility in female population. Environmental and genetic factors are involved. However; etiology of PCOS still remains debatable. Primary Ovarian Insufficiency (POI) or Premature Ovarian Failure (POF) affects 1- 2% of women, and is characterized by amenorrhea before the age of 40 years. POI is heritable in up to 30% of individuals. Methodology: The study presented in the dissertation describes clinical and genetic analysis of twelve Pakistani infertile families (A-L) exhibiting azoospermia, POF, PCOS, Y chromosome microdeletions and chromosomal aberrations. These families were collected from different districts of Khyber Pakhtunkhwa Pakistan. Informed consents were taken from all the participants. Results: In this study, we investigated four azoospermic families (A-D) by whole exome sequencing (WES) analysis. WES data analysis of family A with two males with obstructive azoospermia and two fertile members (mother and brother) revealed a novel nonsense variant c.2326C>T (p.R776X) in dominant X-linked ADGRG2. WES data analysis and Sanger sequencing of family B with one azoospermic male, one fertile brother and parents revealed a compound heterozygous variant in AFF4, including c.3319A>G (p.T1107A). In family C one proband and parents samples were subjected for WES analysis, but no pathogenic variants were identified. WES data analysis of family D with one infertile brother, one fertile brother and parents revealed a novel nonsense variant c.646G>A (p.G216R) in X-linked AR. In family E, WES was performed for four family members and seven potential variants were identified but Sanger sequencing failed to confirm any pathogenic variant. Family F has two daughters displaying primary amenorrhea, elevated LH/FSH levels, atrophic uteri, reduced ovarian reserves, and normal 46XX karyotypes. WES analysis of five family members (parents, two affected daughters and one unaffected daughter) revealed a novel frame shift variant (c.709delC, p.Leu237fs) in the luteinizing hormone/choriogonadotropin receptor (LHCGR) gene. PCOS Families G, H and I were investigated for pathogenic variants. SNP microarray and WES analysis failed to identify pathogenic variants in PCOS families. Family J showed Y chromosome microdeletions (AZFc) in two azoospermic brothers. Families K and L exhibited chromosomal aberrations; OX and XXY karyotypes in azoospermic members in families respectively. Conclusion: Four families revealed novel variants as the likely cause of infertility (ADGRG2, nonsense variant (c.2326C>T); AR nonsense variant (c.646G>A); AFF4 compound heterozygous (c.3319A>G); LHCGR, frame-shift variant (c.709delC). WES in four families (three PCOS one POF) families could not identify genetic causes in the coding region. One family exhibited “Y” chromosome microdeletion (AZFc region deletion) and two families were found with chromosomal aberrations (XXY and OX).