Nonsyndromic oculocutaneous Albinism (nsOCA) is clinically characterized by the loss of pigmentation in the skin, hair, and iris. OCA is amongst the most common causes of vision impairment in children. To date, pathogenic variants in six genes have been identified in individuals with nsOCA. Here, we determined the identities, frequencies, and clinical consequences of OCA alleles in 94 previously unreported Pakistani families. Combination of Sanger and Exome sequencing revealed 38 alleles, including 22 novel variants, segregating with nsOCA phenotype in 80 families. Variants of TYR and OCA2 genes were the most common cause of nsOCA, occurring in 43 and 30 families, respectively. Twenty-two novel variants include nine missense, four splice site, two non-sense, one insertion and six gross deletions. In vitro studies revealed retention of OCA proteins harboring novel missense alleles in the endoplasmic reticulum (ER) of transfected cells. Exon-trapping assays with constructs containing splice site alleles revealed errors in splicing. As eight alleles account for approximately 56% (95% CI: 46.52–65.24%) of nsOCA cases, primarily enrolled from Punjab province of Pakistan, hierarchical strategies for variant detection would be feasible and cost-efficient genetic tests for OCA in families with similar origin. Thus, we developed Tetra-primer ARMS assays for rapid, reliable, reproducible and economical screening of most of these common alleles.
Autosomal recessive primary microcephaly is a rare genetic disorder that is characterized by reduced head circumference and a varying degree of intellectual disability. Genetic studies on consanguineous families with primary microcephaly have identified 15 (MCPH) causative genes that include MCPH1, WDR62, CDK5RAP2, CASC5, ASPM, CENPJ, STIL, CEP135, CEP152, ZNF335, PHC1, CDK6, CENPE, SASS6 MFSD2A ANKLE2 and CIT (Khan et al. 2014; Yamamoto et al. 2014; Alakbarzade et al. 2015;Morris-Rosendahl and Kaindl 2015; Basit et al. 2016). Physiologically, most of these MCPH proteins are involved in cell cycle and its regulation. In the present clinical genetic study, we have present two consanguineous Pakistani families segregating primary microcephaly and intellectual disability. These families were ascertained from the Saraiki ethnic part of Khyber-Pakhtunkhwa province in Pakistan. Whole exome sequencing in one family revealed a novel 1-bp deletion NM_018136.4: c.10013delA (p.Asp3338Valfs*2), while the other family showed a previously reported nonsense mutation NM_018136.4: c.9730C>T (rs199422195 (p.Arg3244*)) in ASPM gene. The novel frame-shift mutation (p.Asp3338Valfs*2) in ASPM presumably truncates the protein synthesis that results in loss of armadillo-type fold domain.
Oculocutaneous albinism (OCA) is an autosomal-recessive disorder of a defective melanin pathway. The condition is characterized by hypopigmentation of hair, dermis, and ocular tissue. Genetic studies have reported seven nonsyndromic OCA genes, among which Pakistani OCA families mostly segregate TYR and OCA2 gene mutations. Here in the present study, we investigate the genetic factors of eight consanguineous OCA families from Pakistan. Genetic analysis was performed through single-nucleotide polymorphism (SNP) genotyping (for homozygosity mapping), whole exome sequencing (for mutation identification), Sanger sequencing (for validation and segregation analysis), and quantitative PCR (qPCR) (for copy number variant [CNV] validation). Genetic mapping in one family identified a novel homozy- K E Y W O R D Sgenetic screening, homozygosity-by-descent mapping, hypopigmentation, melanin, oculocutaneous albinism, SNP genotyping, whole-exome sequencing 278
Plant ethnoveterinary uses are evident in various studies around the world, but the ethnoveterinary practices of forage species are not widely reported. Traditional knowledge is rapidly disappearing because of urbanization and commercial activities. The purpose of this study was to document plant species used by the local communities in Malakand Agency, Pakistan for foraging and ethnoveterinary purposes. Twenty different localities in the study area were surveyed for documentation of forage species and related traditional ethnoveterinary knowledge used for livestock. Semistructured questionnaires and field walks were used to conduct 67 interviews with local farmers and herdsmen. A total of 91 forage species from 26 families were documented, as well as their ethnoveterinary applications. Poaceae and Fabaceae were dominant families with 45% and 15% of species respectively. Among the forage species documented, 62 were highly palatable, 26 were moderately palatable and 12 were less palatable. The region's major veterinary diseases are flu, ringworms, inflammations, low milk production, constipation, bloat, mastitis, pneumonia and wounds. The 62 forage species were reported for the first time for various veterinary uses. This study revealed that local communities commonly use a diverse range of forage species in conjunction with indigenous knowledge of ethnoveterinary uses. These forage species have the potential to overcome the recent fodder shortage. Such studies will be beneficial to the commercial production of such forage species.
Authors' Contribution SSH and SN planned the research work and wrote the manuscript. SN, IA, AK and AUR conducted the research work. RK, SUK and NN collected the samples. SK and MK analyzed the data and revised the manuscript.
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