University of Health Sciences, Lahore.
Lahore, Punjab | Pakistan
Main Specialties: Medical Genetics
Additional Specialties: Human Genetics, Genetic Testing & counseling, Molecular Biology.
Ann Hum Genet 2019 Jul 19;83(4):214-219. Epub 2019 Mar 19.
University of Health Sciences, Lahore, 54600, Pakistan.
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Pak J Pharm Sci 2019 May;32(3 (Supplementary)):1145-1154
Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan.
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Pure and Applied Biology.
Captive breeding is a process of raring the endangered species in man controlled environment like wild life parks, breeding centers and zoos. The present study was carried out to determine the reproductive and breeding performance of peafowls in captivity at Jallo Breeding Center, Lahore. Moreover, the study will also include the mortality causes of these birds. The data was collected from record registers and staff of captive breeding center of Jallo Park Lahore from (2009-2012) of 6 species of peafowls. Our findings revealed that average hatchability in six species was 33.5% in 2009, 61.5% in 2010, 54%in 2011 and 47.8% in 2012. The survival percentage in peafowls was 37.1% in 2009, 94.3% in 2010, 89.1% in 2011 and 81.6% in 2012. Our findings indicated that most of the deaths in Peafowls were not investigated either due to putrefied bodies or missing reports (In Pavo cristatus 47%, in Pavo cristatus mut.nigripennis 75%, in Pavo cristus mut.alba 74%, in Pavo muticus muticus 48% , in Pavo muticus 63% and in Pavo cristatus mut.pied, 79% deaths were not documented). The average deaths recorded by the breeding center (32.67%) were mainly caused by new castle disease virus (NDV), Enteritis, Hemorrhagic Enteritis, Hepatitis + NDV, Traumatic Gizzard, respiratory and heart failure. Taken together, the unhatchability of peafowl eggs and survival of chicks were quite low in captivity. Most of the deaths were not reported either due to putrefied bodies or missing reports.
Waryah YM, Iqbal M, Sheikh SA, Baig MA, Narsani AK, Atif M, Bhinder MA, Rahman A, Memon AI, Pirzado MS, Waryah AM. Two novel variants in CYP1B1 gene: a major contributor of autosomal recessive primary congenital glaucoma with allelic heterogeneity in Pakistani patients. Int J Ophthalmol 2019;12(1):8
Int J Ophthalmol.
Aim: To find the mutations associated with primary congenital glaucoma (PCG) in Pakistani consanguineous pedigrees.
Methods: After getting informed consent, 11 consanguineous pedigrees belonging to different ethnic groups were enrolled. Detailed medical history was recorded and pedigrees were drawn. The standard ophthalmological examination was done to characterize the phenotype. Genomic DNA was extracted from 10 mL whole blood and coding exons and exon intron boundaries of gene were directly sequenced. Bioinformatics tools were used to model the mutant protein and predict the effect of novel variants on protein structure and function.
Results: Sequencing analysis revealed 5 different variants in 7 families (7/11; 64%), including two novel variants. A common mutation, p.R390H was found in four families, whereas p.P437L was found once in a family. Two novel variants, a homozygous non sense variant p.L13* and a compound heterozygous variant, p.P350T along with p.V364M were segregating with PCG in two families. All the patients had the variable onset and severity of the disease. The success rate of early clinical interventions was observed dependent on mutation types and position. Two different haplotypes were associated with frequently found mutation, p.R390H.
Conclusion: Identification of novel variants reassert the genetic heterogeneity of Pakistani PCG patients. The patients with missense mutations show severe phenotypic presentations and poor vision after surgical interventions as compare to patients with null variants. This may help to better understand the role of mutations in the development of PCG and its course of pathogenicity.
Turk J Med Sci 2018 Jun 14;48(3):611-614. Epub 2018 Jun 14.
Background/aim: Genetic variation, an authentic tool of individual discrimination, is being used for forensic investigations worldwide. A missing result for even one out of 13-17 markers leads to an inconclusive report. Additional reliable markers are required to compensate such deficiencies. The SE33 locus has high genetic variability in different populations and is being used in forensic investigation systems in some countries. The purpose of the study was to assess the viability of use of the SE33 locus as a supportive marker for forensic DNA profiling. Materials and methods: Amplification of the SE33 locus was performed using the PowerPlex ES Monoplex System SE33 (Promega). After genotyping 204 Pakistani individuals, different genetic and forensic parameters for the SE33 locus were studied. Results: Genotyping of the SE33 locus revealed a total of 43 alleles including 3 novel alleles. Significant values of different forensic and genetic parameters including power of discrimination, power of exclusion, and polymorphism information content were observed. Conclusions: Addition of the SE33 locus in forensic DNA profiling may help to produce conclusive reports where results are inconclusive due to degraded evidence samples. The SE33 locus can confidently be used for Pakistani and neighboring populations having common ancestors from Iran to Central Asia, the Middle East, India and Turkey.
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J Pediatr Endocrinol Metab 2017 Oct;30(11):1203-1210
Background: Fructose-1,6-bisphosphatase (FBPase) deficiency is a rare inherited metabolic disorder characterized by recurrent episodes of hypoglycemia, ketosis and lactic acidosis. FBPase is encoded by FBP1 gene and catalyzes the hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate in the last step of gluconeogenesis. We report here FBP1 mutations in nine consanguineous Pakistani families affected with FBPase deficiency.
Methods: Nine families having one or two individuals affected with FBPase deficiency were enrolled over a period of 3 years. All FBP1 exonic regions including splicing sites were PCR-amplified and sequenced bidirectionally. Familial cosegregation of mutations with disease was confirmed by direct sequencing and PCR-RFLP analysis.
Results: Three different FBP1 mutations were identified. Each of two previously reported mutations (c.472C>T (p.Arg158Trp) and c.841G>A (p.Glu281Lys)) was carried by four different families. The ninth family carried a novel 4-bp deletion (c.609_612delAAAA), which is predicted to result in frameshift (p.Lys204Argfs*72) and loss of FBPase function. The novel variant was not detected in any of 120 chromosomes from normal ethnically matched individuals.
Conclusions: FBPase deficiency is often fatal in the infancy and early childhood. Early diagnosis and prompt treatment is therefore crucial to preventing early mortality. We recommend the use of c.472C>T and c.841G>A mutations as first choice genetic markers for molecular diagnosis of FBPase deficiency in Pakistan.
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J Genet Disord. Vol.1 No.1:08
Journal of Genetic Disorders
Consanguineous marriage is a marriage between two individuals who are related as second cousins or closer. Consanguineous marriages, traditional and honorable in many parts of the world, are more common in societies with closed economy and societies living a nomadic life . Many religious, cultural, social, political, and economic factors attract the families to prefer consanguineous marriages. More than one billion people of the world are living in communities with preference of consanguineous marriages . Consanguineous marriages may cause increase in autosomal recessive inherited disorders. Plenty of scientific studies in international health literature designate the consanguinity as associated with hundreds of genetic disorders. Autosomal recessive disorders have been observed more than twice as common in consanguineous marriages as in nonconsanguineous. Consanguineous marriages increase the genomic homozygosity in the offspring’s which is mainly responsible for promoting recessive disorders.
Consanguineous matings may pool deleterious lethal alleles in homozygous form to progeny which may cause prenatal, neonatal and child morbidity or mortality . Meta-analysis technique has also supported the increment of disease risk in progeny . Most important medical inference of consanguineous marriages is the increased birth rate of infants with inherited genetic disorders [6,7]. Increased rate of spontaneous abortions, childhood deaths, cerebral palsy and Mediterranean fever have been reported to be high in consanguineous marriages . Rate of birth defects is reported to be substantially high in cousin marriages as compared to the general population . Consanguinity is considered to be an important risk factor for several inborn errors of metabolism and structural deformities . Higher rates of morbidity and mortality have been observed in such cases. First cousins marriages illustrate a 1.5 to 3% increased risk of having a child with inborn errors of metabolism while the double first cousins show twofold risk than of first cousin matings.
Some reports suggest the association of consanguinity with inherited immunodeficiency disorders. Relationship of cousin marriages with some other inherited disorder like slow birth weight, protein-C and protein-S deficiency, beta-thalassemia, children’s hypertension and phenylketonuria has also been evidenced by many researchers . Hearing loss, the most common sensorineural illness in developed countries  has been proven to be linked with consanguinity. Numerous diseases related to vision impairment have been evidenced to be affected by consanguinity. Some studies have linked consanguinity with increased incidence of some infectious diseases like TB and hepatitis. Increased infection risk has also been found to be associated with consanguinity in animal populations . The prevalence of common adult diseases such as diabetes mellitus, cancer, blood disorders, mental disorders, some heart diseases, asthma, gastro-intestinal disorders, hypertension, hearing deficit, G6PD and common eye diseases has also been observed to be influenced by consanguinity. Significantly higher rates of epilepsy have been recorded among family members with consanguineous marriages . In a recent study, parental consanguinity has been proved to be associated with early age of onset of schizophrenia . Relationships between consanguinity and complex multifactorial disorders of adulthood have not been studied significantly. Only a few reports support the existence of association of consanguinity with complex multifactorial diseases. Effects of consanguinity on fertility are controversial. Some studies relate consanguinity with infertility; others deny existence of any relationship between them. Both positive and negative associations with consanguinity have been reported in breast cancer and heart diseases.
Prevalence of consanguineous marriages is high in those regions of the world which lack education and awareness. Strategies and plans should be devised to raise the education level and social awareness about consanguineous marriages. Participation of youth and parents in awareness campaign should be assured to increase its effectiveness. Genetic consultancy may play an imperative role in those populations where consanguineous marriages are unavoidable. Epidemiological studies and scientific surveys are necessary to explore a possible relationship of consanguinity with other diseases. Biomedical research should have a commitment to integrate genomic medicine into future health services. Premarital screening for determination of genetic risks in progeny may help guide to have better matrimonial choice within family. For early diagnosis and management prenatal and postnatal screening programs for genetic diseases would be beneficial in the regions of high consanguinity rates. Consanguineous communities, at high risk of diseases, should be identified and debate on consanguinity related cultural and religious beliefs should be promoted.
J Coll Physicians Surg Pak. 2017 May;27(5):308-310
Journal of the College of Physicians and Surgeons Pakistan
Junctional epidermolysis bullosa (JEB) is a recessively inherited skin blistering disease and is caused due to abnormalities in proteins that hold layers of the skin. Herlitz JEB is the severe form and non-Herlitz JEB is the milder form. This report describes a case of congenitally affected male child aged 5 years, with skin blistering. He has mitten-like hands and soft skin blistering on hands, legs and knees. Symptoms almost disappeared at the age of 3 years but reappeared with increased severity after 6 months. Histopathological examination showed epidermal detachment with intact basal cell layer and sparse infiltrate of lymphocytes with few eosinophils in the dermis. There was no blistering on the moist lining of the mouth and digestive tract. Localized symptoms with less lethality and histopathological examination indicated the presence of non-Herlitz type of JEB. This is the first report which confirms the presence of non-Herlitz junctional epidermolysis bullosa in Pakistan.
Asian Journal of Natural & Applied Sciences. 5(3) Pages: 28-37
Asian Journal of Natural & Applied Sciences
Mental Retardation (MR) is a heterogeneous group of disorders characterized by a significant impairment of cognitive and development due to abnormalities in the structure or function of brain. Mentally Retarded persons have IQ less than 70. The worldwide prevalence of MR is 1-3%. A number of factors including environmental factors, genetic factors, malnutrition, maternal use of alcohol during pregnancy, drug and poverty are responsible for MR. The congenital dysfunction of brain and injury of brain can also cause MR. The leading cause of MR births include Fetal Alcohol Syndrome, Down’s syndrome and metabolic disorders like PKU.
J Pediatr Endocrinol Metab 2016 Mar;29(3):327-32
Background: Hereditary tyrosinemia type 1 (HT1) is a rare inborn error of tyrosine catabolism with a worldwide prevalence of one out of 100,000 live births. HT1 is clinically characterized by hepatic and renal dysfunction resulting from the deficiency of fumarylacetoacetate hydrolase (FAH) enzyme, caused by recessive mutations in the FAH gene. We present here the first report on identification of FAH mutations in HT1 patients from Pakistan with a novel one.
Methods: Three Pakistani families, each having one child affected with HT1, were enrolled over a period of 1.5 years. Two of the affected children had died as they were presented late with acute form. All regions of the FAH gene spanning exons and splicing sites were amplified by polymerase chain reaction (PCR) and mutation analysis was carried out by direct sequencing. Results of sequencing were confirmed by restriction fragment length polymorphism (PCR-RFLP) analysis.
Results: Three different FAH mutations, one in each family, were found to co-segregate with the disease phenotype. Two of these FAH mutations have been known (c.192G>T and c.1062+5G>A [IVS12+5G>A]), while c.67T>C (p.Ser23Pro) was a novel mutation. The novel variant was not detected in any of 120 chromosomes from normal ethnically matched individuals.
Conclusions: Most of the HT1 patients die before they present to hospitals in Pakistan, as is indicated by enrollment of only three families in 1.5 years. Most of those with late clinical presentation do not survive due to delayed diagnosis followed by untimely treatment. This tragic condition advocates the establishment of expanded newborn screening program for HT1 within Pakistan.
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JAPS. 25(3 Supp. 2) 2015 Special Issue Page: 416-422
The Journal of Animal & Plant Sciences,
Bajwat, an internationally important wetland is located in Sialkot district of Pakistan. During one year study the area was regularly visited with supporting materials such as camera, binocular and bird identification books.We have recorded 110 avian species belonging to 73 genera, 39 families and 15 orders. Passeriformes has highest number of species (39) and genera (23) of which the most abundant number of species are from Motacillidae family. Among non-Passeriformes Anatidae family has maximum number of species. We are reporting for the first time the assemblage of eight Aythyaferinaswimming in a line at midday in a male-female-male-female fashion being still in running water. Most of the resident birds were found to be common or abundant while most of the summer visitors were rare and scarce. Control of pollution and habitat destruction is needful. This is the first report of avifauna of the area showing the richness of biodiversity.
Adv. life sci., vol. 1, no. 3, May 2014
Advancements in Life Sciences
Background: Due to high copy number of mitochondria per cell mtDNA testing is often successful in cases where nuclear DNA is highly degraded or the sample source is too limited. Sequence polymorphism of D-loop region of mtDNA has been used for identification of forensic remains, analysis of mother–child relationships and comparisons between ethnic groups through maternal lineages. PCR conditions were optimized and validated for three hypervariable regions (HVR I- 480 bp, HVR II- 420 bp and HVIII- 255 bp) of mitochondria conducted at National Centre of Excellence in Molecular Biology, University of the Punjab – Lahore, Pakistan. Methodology: Blood samples of 86 individuals were drawn from 25 Pakistani families. DNA was extracted and purified by Sambrook method. DNA was quantified at agarose gel electrophoresis and N-D 1000 Nanodrop spectrophotometer. Three hypervariable regions (HVR I, HVR II and HVIII) of mitochondrial DNA were optimized with different PCR components and PCR conditions using three pairs of oligonucleotides along with reagent blanks, positive and negative controls. Results: Three hypervariable regions (HVR I, HVR II and HVIII) of mitochondrial DNA were optimized in the PCR reaction volume at different concentrations of PCR buffer, MgCl2, Taq DNA polymerase, dNTPs, primers and mtDNA template at varying annealing temperatures. The best results for amplification were shown at 1x PCR buffer, 2.5mM Mgcl2, 0.3μl of Taq DNA polymerase (5u/μl), 0.2mM dNTPs, 0.8μM forward-reverse primers for HVR I, 0.7μM forward-reverse primers for HVR II and 0.4μM forward-reverse primers for HVR III at 52◦C annealing temperature. Conclusion: Optimized PCR protocol for three hypervariable mtDNA regions has provided a way out to lead mtDNA analysis which is very necessary tool in those forensic biological samples, where nuclear DNA is highly degraded, to identify missing persons and determine maternal lineages.
Otolaryngol Head Neck Surg 2013 Sep 14;149(3):478-87. Epub 2013 Jun 14.
Divisions of Ophthalmology, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio USA.
Objective: To identify the genetic cause of prelingual sensorineural hearing loss in Pakistani families using a next-generation sequencing (NGS)-based mutation screening test named OtoSeq.
Study Design: Prospective study.
Setting: Research laboratory.
Subjects And Methods: We used 3 fluorescently labeled short tandem repeat (STR) markers for each of the known autosomal recessive nonsyndromic (DFNB) and Usher syndrome (USH) locus to perform a linkage analysis of 243 multigenerational Pakistani families segregating prelingual hearing loss. After genotyping, we focused on 34 families with potential linkage to MYO7A, CDH23, and SLC26A4. We screened affected individuals from a subset of these families using the OtoSeq platform to identify underlying genetic variants. Sanger sequencing was performed to confirm and study the segregation of mutations in other family members. For novel mutations, normal hearing individuals from ethnically matched backgrounds were also tested.
Results: Hearing loss was found to co-segregate with locus-specific STR markers for MYO7A in 32 families, CDH23 in 1 family, and SLC26A4 in 1 family. Using the OtoSeq platform, a microdroplet PCR-based enrichment followed by NGS, we identified mutations in 28 of the 34 families including 11 novel mutations. Sanger sequencing of these mutations showed 100% concordance with NGS data and co-segregation of the mutant alleles with the hearing loss phenotype in the respective families.
Conclusion: Using NGS-based platforms like OtoSeq in families segregating hearing loss will contribute to the identification of common and population-specific mutations, early diagnosis, genetic counseling, and molecular epidemiology.
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J Hum Genet 2011 Jul 2;56(7):534-40. Epub 2011 Jun 2.
National Center of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
There are 68 sex-linked syndromes that include hearing loss as one feature and five sex-linked nonsyndromic deafness loci listed in the OMIM database. The possibility of additional such sex-linked loci was explored by ascertaining three unrelated Pakistani families (PKDF536, PKDF1132 and PKDF740) segregating X-linked recessive deafness. Sequence analysis of POU3F4 (DFN3) in affected members of families PKDF536 and PKDF1132 revealed two novel nonsense mutations, p.Q136X and p.W114X, respectively. Family PKDF740 is segregating congenital blindness, mild-to-profound progressive hearing loss that is characteristic of Norrie disease (MIM#310600). Sequence analysis of NDP among affected members of this family revealed a novel single nucleotide deletion c.49delG causing a frameshift and premature truncation (p.V17fsX1) of the encoded protein. These mutations were not found in 150 normal DNA samples. Identification of pathogenic alleles causing X-linked recessive deafness will improve molecular diagnosis, genetic counseling and molecular epidemiology of hearing loss among Pakistanis.
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Clin Genet 2009 Mar;75(3):237-43
Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA.
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Clin Genet 2009: 75: 237–243
Mutations in OTOF, encoding otoferlin, cause non-syndromic recessive hearing loss. The goal of our study was to define the identities and frequencies of OTOF mutations in a model population. We screened a cohort of 557 large consanguineous Pakistani families segregating recessive, severe-to-profound, prelingual-onset deafness for linkage to DFNB9. There were 13 families segregating deafness consistent with linkage to markers for DFNB9. We analyzed the genomic nucleotide sequence of OTOF and detected probable pathogenic sequence variants among all 13 families. These include the previously reported nonsense mutation p.R708X and 10 novel variants: 3 nonsense mutations (p.R425X, p.W536X, and p.Y1603X), 1 frameshift (c.1103_1104delinsC), 1 single amino acid deletion (p.E766del) and 5 missense substitutions of conserved residues (p.L573R, p.A1090E, p.E1733K, p.R1856Q and p.R1939W). OTOF mutations thus account for deafness in 13 (2.3%) of 557 Pakistani families. This overall prevalence is similar, but the mutation spectrum is different from those for Western populations. In addition, we demonstrate the existence of an alternative splice isoform of OTOF expressed in the human cochlea. This isoform must be required for human hearing because it encodes a unique alternative C-terminus affected by some DFNB9 mutations.