Genomic selection pressure discovery using site-frequency spectrum and reduced local variability statistics in Pakistani Dera-Din-Panah goat.

BACKGROUND: Population geneticists have long sought to comprehend various selection traces accumulated in the goat genome due to natural or human driven artificial selection through breeding practices, which led the wild animals to domestication, so understanding evolutionary process may helpful to utilize the full genetic potential of goat genome. METHODS AND RESULTS: As a step forward to pinpoint the selection signals in Pakistani Dera-Din-Panah (DDP) goat, whole-genome pooled sequencing (n = 12) was performed, and 618,236,192 clean paired-end reads were mapped against ARS1 reference goat assembly. Five different selection signature statistics were applied using four site-frequency spectrum (SFS) methods (Tajima's D ([Formula: see text]), Fay and Wu's H ([Formula: see text]), Zeng's E ([Formula: see text]), [Formula: see text]) and one reduced local variability approach named pooled heterozygosity ([Formula: see text]). The under-selection regions were annotated with significant threshold values of [Formula: see text]≥4.7, [Formula: see text]≥6, [Formula: see text]≥2.5, Pool-HMM ≥ 12, and [Formula: see text]≥5 that resulted in accumulative 364 candidate gene hits. The highest genomic selection signals were observed on Chr. 4, 6, 10, 12, 15, 16, 18, 20, and 27 and harbor ADAMTS6, CWC27, RELN, MYCBP2, FGF14, STIM1, CFAP74, GNB1, CALML6, TMEM52, FAM149A, NADK, MMP23B, OPN3, FH, MFHAS1, KLKB1, RRM1, KMO, SPEF2, F11, KIT, KMO, ERI1, ATP8B4, and RHOG genes. Next, the validation of our captured genomic hits was also performed by more than one applied statistics which harbor meat production, immunity, and reproduction associated genes to strengthen our hypothesis of under-selection traits in this Pakistani goat breed. Furthermore, common candidate genes captured by more than one statistical method were subjected to gene ontology and KEGG pathway analysis to get insights of particular biological processes associated with this goat breed. CONCLUSION: Current perception of genomic architecture of DDP goat provides a better understanding to improve its genetic potential and other economically important traits of medium to large body size, milk, and fiber production by updating the genomic insight driven breeding strategies to boost the livestock and agriculture-based economy of the country.

Gastric Staple Line Reinforcement With Ligation Clips for Hemostasis in Laparoscopic Sleeve Gastrectomy.

INTRODUCTION: In Pakistan and worldwide, there is a lack of literature on the role of ligation clips in controlling hemostasis in laparoscopic sleeve gastrectomy. ligation clips are being used to secure hemostasis and act as staple line reinforcement to prevent intra-operative and postoperative bleeding. Data can be utilized to reflect the role of staple line reinforcement with ligation clips so as to guide surgeons about its safety and efficacy. METHODOLOGY: This retrospective observational study was conducted at the Shalamar Hospital, Lahore, Pakistan, and included 120 patients. The patients' demographic parameters, BMI, intra-operative and postoperative bleeding in terms of hematemesis, melena, and fall in hemoglobin (Hb) postoperatively were compared to preoperative Hb and recorded. RESULT: One hundred and twenty cases of laparoscopic sleeve gastrectomy (LSG) were included with a mean age of 44.77±12.05 years. The mean BMI was 52.06±13.85 preoperatively. The mean drop in hemoglobin was 0.04±0.26 with a p-value of 0.07, which is statistically insignificant. Among 120 cases, two (1.7%) patients reported episodes of melena, and four (3.3%) patients reported hematemesis. Postoperative hypotension was recorded in six (5%) patients and eight (6.7%) patients had postoperative tachycardia. CONCLUSION: This study shows ligation clip application along the staple line is an effective means of hemostasis similar to suture application.

Detection of whole genome selection signatures of Pakistani Teddy goat.

BACKGROUND: Natural and artificial selection tend to cause variability that contributes to shape the genome of livestock in a way that differentiates them among the animal kingdom. The particular aim here is to identify positive selection signatures with whole genome pooled-sequence data of Pakistani Teddy goat. METHODS AND RESULTS: Paired-end alignment of 635,357,043 reads of Teddy goat with (ARS1) reference genome assembly was carried out. Pooled-Heterozygosity (Hp) and Tajima's D (TD) are applied for validation and getting better hits of selection signals, while pairwise FST statistics is conducted on Teddy vs. Bezoar (wild goat ancestor) for genomic differentiation, moreover annotation of regions under positive selection was also performed. Hp score with - ZHp > 5 detected six windows having highest hits on Chr. 29, 9, 25, 15 and 14 that harbor HRASLS5, LACE1 and AXIN1 genes which are candidate for embryonic development, lactation and body height. Secondly, - ZTD value of > 3.3 showed 4 windows with very strong hits on Chr.5 & 9 which harbor STIM1 and ADM genes related to body mass and weight. Lastly, - ZFST < - 5 generated four strong signals on Chr.5 & 12 harbor LOC102183233 gene. Other significant selection signatures encompass genes associated with wool production, prolificacy and coat colors traits in this breed. CONCLUSIONS: In brief, this study identified the genes under selection in Pakistani Teddy goat that will be helpful to refining the marker-assisted breeding policies and converging required production traits within and across other goat breeds and to explore full genetic potential of this valued species of livestock.

Whole genome comparison of Pakistani Corona virus with Chinese and US Strains along with its predictive severity of COVID-19.

Initially submitted 784 SARS-nCoV2 whole genome sequences on NCBI Virus database were selected for phylogenetic analysis to look into their similarities with two of Pakistani sequenced coronavirus strains having accessions of MT240479 and MT262993. The MT240479 named (Gilgit1-Pak) was found in close proximity to MT184913 named (CruiseA-USA), while MT262993 named (Manga-Pak) was in neighboring to MT039887 named (WI-USA) strain, which were further chosen for variant calling analysis along with reference genome NC_045512 as out-group to construct concluding cladogram and looked for evolutionary distance with PAUP software in this article. Aforementioned Pakistani strains each of having 29,836 bases were compared with MT263429 (WI-USA) of 29,889 bases and MT259229 (Wuhan-P.R. China) of 29,864 bases. Whole genome variant calling pipeline revealed 31 variants in both Pakistani strains collectively (Manga-Pak vs USA having 2del & 7SNPs, while different from Chinese strain with 2del & 2SNPs, similarly Gilgit1-Pak vs USA having 10SNPs, while different from Chinese strains having 8SNPs). These variants harbour ORF1ab, ORF1a and N genes having their role is viral replication/translation, host innate immunity and viral capsid formation respectively. These novel variants may be one of the reasons for low mortality rate in Pakistan with 385 deaths as compared to USA with 63,871 and P.R. China with 4633 by May 01, 2020. However functional characterization of these variants and their integrations with other viral proteins including variability of human receptors (ACE2 & NRP1) may be the other reasons for unlikely COVID-19 statistics in Pakistan which need further confirmatory studies. Moreover, mutated N and ORF1a proteins in Pakistani strains were also analyzed by 3D structure modeling, which give another dimension of comparing these alterations at amino acid level. In a nutshell, these novel variants are correlated with reduced mortality of COVID-19 severity in Pakistan while more robust results can be obtained by wet lab experimentation. This also gives insight of genomic landscape of these indigenous strains to develop diagnostics kits, vaccines and therapeutic interventions.