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Due to its geo strategic position at the crossroad of Asia, Pakistan has gained crucial importance of playing its pivotal role in subsequent human migratory events, both prehistoric and historic. This human movement became possible through an ancient overland network of trails called “The Silk Route” linking Asia Minor, Middle East China, Central Asia and Southeast Asia. This study was conducted to analyze complete mitochondrial control region samples of 100 individuals of four major Pashtun tribes namely, Bangash, Khattak, Mahsuds and Orakzai in the province of Khyber Pakhtunkhwa, Pakistan. All Pashtun tribes revealed high genetic diversity which is comparable to the other Central Asian, Southeast Asian and European populations. The configuration of genetic variation and heterogeneity further unveiled through Multidimensional Scaling, Principal Component Analysis and phylogenetic analysis. The results revealed that Pashtun are the composite mosaic of West Eurasian ancestry of numerous geographic origin. They received substantial gene flow during different invasive movements and have a high element of the Western provenance. The most common haplogroups reported in this study are: South Asian haplogroups M (28%) and R (8%); whereas, West Asians haplogroups are present, albeit in high frequencies (67%) and widespread over all; HV (15%), U (17%), H (9%), J (8%), K (8%), W (4%), N (3%) and T (3%). Moreover, we linked the unexplored genetic connection between Ashkenazi Jews and Pashtun. The presence of specific haplotypes J1b (4%) and K1a1b1a (5%) pointed to a genetic connection of Jewish conglomeration in Khattak tribe. This was a result of an ancient genetic influx in the early Neolithic period that led to the formation of a diverse genetic substratum in present day Pashtun. [ABSTRACT FROM PUBLISHER]

An abstract of the article "Genetic Susceptibility of HCV RNA and its genotypic distribution in Punjab, Pakistan," by G. Rubi and M. Aslamkhan is presented.

Increasing data show that intronic derived regulatory elements, such as transcription factor binding sites (TFBs), play key roles in gene regulation, and malfunction. Accordingly, characterizing the sequence context of the intronic regions of the human coagulation factor VIII ( hFVIII ) gene can be important. In this study, the intronic regions of the hFVIII gene were scrutinized based on in-silico methods. The results disclosed that these regions harbor a rich array of functional elements such as repetitive elements (REs), splicing sites, and transcription factor binding sites (TFBs). Among these elements, TFBs and REs showed a significant distribution and correlation to each other. This survey indicated that 31% of TFBs are localized in the intronic regions of the gene. Moreover, TFBs indicate a strong bias in the regions far from splice sites of introns with mapping to different REs. Accordingly, TFBs showed highly bias toward Short Interspersed Elements (SINEs), which in turn they covering about 12% of the total of REs. However, the distribution pattern of TFBs-REs showed different bias in the intronic regions, spatially into the Introns 13 and 25. The rich array of SINE-TFBs and CR1-TFBs were situated within 5'UTR of the gene that may be an important driving force for regulatory innovation of the hFVIII gene. Taken together, these data may lead to revealing intronic regions with the capacity to renewing gene regulatory networks of the hFVIII gene. On the other hand, these correlations might provide the novel idea for a new hypothesis of molecular evolution of the FVIII gene, and treatment of Hemophilia A which should be considered in future studies., (© 2020 The Authors.)

To investigate the uniparental genetic structure of the Punjabi population from mtDNA aspect and to set up an appropriate mtDNA forensic database, we studied maternally unrelated Punjabi (N = 100) subjects from two caste groups (i.e. Arain and Gujar) belonging to territory of Punjab. The complete control region was elucidated by Sanger sequencing and the subsequent 58 different haplotypes were designated into appropriate haplogroups according to the most recently updated mtDNA phylogeny. We found a homogenous dispersal of Eurasian haplogroup uniformity among the Punjab Province and exhibited a strong connotation with the European populations. Punjabi castes are primarily a composite of substantial South Asian, East Asian and West Eurasian lineages. Moreover, for the first time we have defined the newly sub-haplogroup M52b1 characterized by 16223 T, 16275 G and 16438 A in Gujar caste. The vast array of mtDNA variants displayed in this study suggested that the haplogroup composition radiates signals of extensive genetic conglomeration, population admixture and demographic expansion that was equipped with diverse origin, whereas matrilineal gene pool was phylogeographically homogenous across the Punjab. This context was further fully acquainted with the facts supported by PCA scatterplot that Punjabi population clustered with South Asian populations. Finally, the high power of discrimination (0.8819) and low random match probability (0.0085%) proposed a worthy contribution of mtDNA control region dataset as a forensic database that considered a gold standard of today to get deeper insight into the genetic ancestry of contemporary matrilineal phylogeny.

Androgen mediating signaling is implicated in regulating the expression of reproductive related genes. Any deviation in the gene expression might be the ignitable precursor for genomic instability that inflames the genomic rearrangements and a leading cause of cancer. The main goal of this study was to determine the relationships between trinucleotide repeats of androgen receptor (AR), sex steroids, and sexual function in men presenting with reduced sperm motility. We investigated the singleton or combinatorial effects of the length of trinucleotide repeats of AR on reproductive hormones, clinical parameters, semen analyses, as well as sexual assessment function of 210 asthenospermic outpatients along with 125 normal subjects. Sexual assessment was executed using the International Index of Erectile Function (IIEF-15 score) which measures erectile function (EF), orgasmic function (OR), sexual desire (SD), intercourse satisfaction (IS), and overall satisfaction. Our findings suggest that long (>26 CAG)n repeats have an inverse correlation with circulatory FSH and T, whereas long (>25 GGC)n repeats have moderated affiliation with reduced sperm concentration. The study revealed a novel finding by exploring the negative correlation between elongated (CAG)n repeats and the cumulative IIEF-15 score, orgasm function (OR), and erectile function (EF) in asthenospermic men. This study examines the tri-nucleotide correlation with sexual function in Punjabi men enhancing our understanding of the regulatory mechanisms of sexual performance., Abbreviations: AR: androgen receptor; IIEF-15 score: International Index of Erectile Function; EF: erectile function; OR: orgasmic function; SD: sexual desire; IS: intercourse satisfaction; FSH: follicular stimulating hormone; T: testosterone; NTD: N-terminal transactivation domain; DBD: DNA-binding domain; LBD: ligand binding domain; TNR: tri-nucleotide repeat.

Background: Despite its worldwide high occurrence, the obscurity regarding the description, epidemiology and management of premature ejaculation remains provocative. It is well established that male premature ejaculatory dysfunction is an increasing problem due to spontaneous ejaculation across a variety of general and clinical subjects. The main goal of this study was to determine the relationships between trinucleotide repeats of the androgen receptor (AR), sex steroids, and pituitary hormones with sexual function in men with type 2 diabetes mellitus (DM) and reported with acquired premature ejaculation (PE)., Methods: A total of 150 normal and 250 PE + DM subjects were enrolled in this study. Each subject was invited to fill out an elaborative questionnaire to acquire precise selective information regarding BMI, duration of PE + DM, self-reported Intra-Vaginal Ejaculatory Latency Time (IELT), sexual and mental health status by using the premature ejaculation diagnostic tool (PEDT) and Beck Depression Inventory-II (BDI-II). Pearson's correlation analysis was used to analyze the relationship between clinical, hormonal, and genetic variables. Ward's minimum variance cluster analysis and principal component analysis were used for evaluation of dependence between genetic, clinical, and demographic parameters., Results: The patients who have the lowest number of (≤21) (CAG)n repeats have higher serum oxytocin levels (114.2 pg/ml; n  = 54, 43.2%) than the controls (69.18 pg/ml; n  = 22, 17.6%) and the patients with the highest (≥26) number of (CAG)n repeats (62.9 pg/ml; n  = 108, 43.2%).On the other hand, patients who have the highest numbers of (CAG)n repeats (≥26) have higher serum testosterone (6.1 ng/ml; n  = 108, 43.2% of cohort) lower prolactin (3.01 ng/ml; n  = 108, 43.2% of cohort) levels than the controls and patients with the lowest numbers (≤21) of (CAG)n repeats and their TSH (1.53 mIU/L, P  < 0.05) levels are lower than those of controls. In the Pearson correlation model, self-estimated IELT demonstrated significantly negative correlation with both (CAG)n and (GCC)n repeats ( r  = - 0.16, p  = 0.0001; r  = - 0.19, p  = 0.0001) respectively. These repeats have positive correlation with PEDT ( r  = 0.28, p  = 0.0001: r  = 0.24, p  = 0.0001, whole model) and inversely correlated with BDI-II ( r  = - 0.25, p  = 0.0001)., Conclusion: This study indicates that androgen receptor polymorphism modulates the endocrine effect on ejaculatory reflex and depends strongly on its "cofactors". Moreover, our results also confirmed an association between long tri-nucleotide repeats of androgen receptor, sex steroids, pituitary, and thyroid hormones in relation to  acquired premature ejaculatory dysfunction in diabetic patients. However, endocrine regulation of PE reflex is a complex phenomenon that requires further investigation., Competing Interests: The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Intellectual disability (ID) is a neurodevelopmental disorder affecting 1%-3% of the population worldwide. It is characterised by high phenotypic and genetic heterogeneity and in most cases the underlying cause of the disorder is unknown. In our study we investigated a large consanguineous family from Baluchistan, Pakistan, comprising seven affected individuals with a severe form of autosomal recessive ID (ARID) and epilepsy, to elucidate a putative genetic cause., Methods and Results: Whole exome sequencing (WES) of a trio, including a child with ID and epilepsy and its healthy parents that were part of this large family, revealed a homozygous missense variant p.R53Q in the lectin mannose-binding 2-like (LMAN2L) gene. This homozygous variant was co-segregating in the family with the phenotype of severe ID and infantile epilepsy; unaffected family members were heterozygous variant carriers. The variant was predicted to be pathogenic by five different in silico programmes and further three-dimensional structure modelling of the protein suggests that variant p.R53Q may impair protein-protein interaction. LMAN2L (OMIM: 609552) encodes for the lectin, mannose-binding 2-like protein which is a cargo receptor in the endoplasmic reticulum important for glycoprotein transport. Genome-wide association studies have identified an association of LMAN2L to different neuropsychiatric disorders., Conclusion: This is the first report linking LMAN2L to a phenotype of severe ARID and seizures, indicating that the deleterious homozygous p.R53Q variant very likely causes the disorder., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: To determine the existence of autosomal recessive deafness loci in different ethnic tribes of the Punjab., Study Design: Descriptive observational study., Place and Duration of Study: Department of Human Genetics and Centre of Excellence in Molecular Biology, University of Health Sciences, Lahore, from July 2009 to March 2012., Methodology: Healthy willing subjects with autosomal recessive deafness loci were studied for selected deafness loci. Those who were unhealthy and gave history of infectious disease were excluded. DNAextraction was carried out using the inorganic method. Fluorescently labeled microsatellite markers were used for amplification of desired regions by PCR (Polymerase Chain Reaction). Automated allele assignment was performed using the ABI PRISM GeneScan Analysis Software Version 3.7 for Windows NTPlatform. Two-point LOD scores were calculated using the FASTLINK computer package (Schaffer 1996) and MLINK was used for calculation and 95% CI (confidence intervals) were calculated., Results: One hundred and thirty two individuals of 8 families were analyzed. Three families (SAPun-03, SAPun-10 and SAPun-15) were found linked to DFNB12; two families (SAPun-05 and SAPun-17) were found linked to DFNB8/10, while three families (SAPun-06, SAPun-13 and SAPun-19) were found linked to DFNB29, DFNB36 and DFNB37 respectively., Conclusion: The genotyping results revealed that DFNB12 locus was the most common followed by DFNB8/10 locus, while the Loci DFNB29, DFNB36 and DFNB37 were less common.

The mating and swarming behaviour of A. culicifacies Giles was investigated during December 1975 at a cattle shed near the village of Sattoki, Lahore District, Punjab, Pakistan. On average, swarming commenced 20.9 min before sunset (light intensity 1414.4 lx) and ended 21.0 min after sunset (5.4 lx) with pairing restricted to the period from 6.1 min before (467.2 lx) to 15.8 min after sunset (26.9 lx). The swarms were principally composed of males, with females entering only for mating. On average, copulation lasted 27.2 s and was completed in flight. Most females (71.8%) collected while mating had taken a partial blood meal either the previous evening or on the same evening as mating. All females in the swarms were nulliparous and 82.6% had ovaries developed to at least Christophers' stage IIa.

All of 704 Cx. tritaeniorhynchus females caught on bufflo bait were inseminated and 98 % were at ovariole stage 1. Parity rates ranged from 41 % to 66 % on the 4 nights studied with increases observed during dusk, midnight and before dawn. Changes in the parity of the biting population were related to sexual maturation, mating, oviposition rhythms and especially the survivorship of the adults.

Anopheles culicifacies that were susceptible, heterozygous, or homozygous resistant to HCH and dieldrin were differentially marked with fluorescent dusts and released twice weekly into village huts in Pakistan that had been sprayed with four different dosages of HCH to see which of the genotypes died and which survived. The three highest dosages killed all three genotypes in the first four weeks, and heterozygotes and susceptibles for at least 12 weeks. The lowest dosage killed all the susceptibles throughout the period, and all but 0.07% of the heterzygotes. Thus the resistance is effectively recessive at the higher dosages and unlikely to be selected rapidly, as long as the gene frequency is low to start with and the houses are sprayed regularly. Similar releases of partially and completely resistant A. stephensi, and completely resistant A. subpictus, showed greater survival rates on exposure to the high HCH dosages than the same genotypes of A. culicifacies.

Annual population curves for C. tritaeniorhynchus are presented for representative localities distributed from Pakistan, east through Southeast Asia and the Philippines and north to Japan and Korea. In the dry temperature (Pakistan) and colder maritime climates (Japan and Korea). C. tritaeniorhynchus populations apparently overwintered as hibernating adults, while in the warmer maritime climates (Okinawa and Taiwan), gonotrophic activity and larval development continued throughout the winter months. In these climatic types, the population curves closely paralleled the annual temperature curves. In the tropical climates, however, temporal population patterns were closely related to available moisture either in the form of annual precipitation and/or rice irrigation. The extremely variable environmental conditions tolerated C. tritaeniorhynchus throughout its distribution attests to the physiological and ecological plasticity of this species and suggests that further ecological and genetic studies may reveal marked clinical variances among selected biological parameters.

10 118 female and 10 863 male Anopheles stephensi were released on three successive nights at a breeding site near the village of Sattoki, Punjab Province, Pakistan during early May, 1977. A total of 721 (7.13%) females and 505 (4.65%) males were recaptured resting indoors, feeding on buffaloes and swarming. The average distance dispersed for females and males recaptured resting inside 13 cattle sheds within 2.17 km of the release point was 165.5 m and 184.8 m, respectively. The maximum longevity of the marked females and males was 12 and 13 days, respectively (mean longevity 3.24 and 3.26 days, respectively). Population size was estimated for the first five days after release using the Lincoln Index modified to account for survivorship, and Jackson's positive and negative methods. Estimates of population size at the two cattle sheds nearest the release point ranged from 1294.7--2551.7 for females and from 481.6--1374.3 for males, considerably less than the size of the released cohort. Marked males from all three releases were collected while swarming with wild males. Inseminated marked and unmarked females were captured at male swarms. Females mated on the night of release, some within 15 minutes of release. Mating here presumably occurred while the females were transversing the 45 metres from the release point to the site of the buffalo biting collections. Both inseminated and uninseminated females were collected feeding on buffaloes. The first gonotrophic cycle was completed when the females were three to four days old, i.e. two to three days after release.