Genome sequencing reveals novel causative structural and single nucleotide variants in Pakistani families with congenital hypogonadotropic hypogonadism
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PROVIDER: PRJEB76310 | ENA |
REPOSITORIES: ENA
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Project description:Latest advancement of omics technologies allows in-depth characterization of venom compositions. In the present work we present a proteomic study of two snake venoms of the genus Naja i.e. Naja naja (black cobra) and Naja oxiana (brown cobra), of Pakistani origin. The present study has shown that these snake venoms consist of a highly diversified proteome. Furthermore, the data also revealed variation among closely related species. High throughput mass spectrometric analysis of the venom proteome allowed to identify for the N. naja venom 34 protein families and for the N. oxiana 24 protein families. The comparative evaluation of the two venoms showed that N. naja consists of a more complex venom proteome than N. oxiana venom.
2020-10-29 | PXD018726 | Pride
Project description:PURPOSE: To identify the disease-causing mutations in three consanguineous Pakistani families with multiple members affected by primary congenital glaucoma. METHODS: Blood samples were collected, and DNA was extracted. Linkage analysis for reported primary congenital glaucoma loci was performed using closely spaced polymorphic microsatellite markers on genomic DNA from affected and unaffected family members. All coding exons, the exon-intron boundaries, and the 5' untranslated region of CYP1B1 were sequenced. RESULTS: The alleles of chromosome 2p markers segregate with the disease phenotype in all three families with positive LOD scores. The sequencing results identified three novel mutations (L177R, L487P, and D374E) and one previously reported mutation (E229K) in CYP1B1 that segregate with the disease phenotype in their respective families. None of these sequence variations were present in 96 ethnically matched control samples. CONCLUSIONS: These results strongly suggest that missense mutations in CYP1B1 are most likely to be responsible for primary congenital glaucoma in these families.
| S-EPMC2579935 | biostudies-literature
Project description:Human gut microbiome of Pakistani population Metagenome
| PRJNA477600 | ENA
Project description:This study was undertaken to investigate the causal mutations responsible for autosomal recessive congenital stationary night blindness (CSNB) in consanguineous Pakistani families.Two consanguineous families with multiple individuals manifesting symptoms of stationary night blindness were recruited. Affected individuals underwent a detailed ophthalmological examination, including fundus examination and electroretinography. Blood samples were collected and genomic DNA was extracted. Exclusion analyses were completed by genotyping closely spaced microsatellite markers, and two-point logarithm of odds (LOD) scores were calculated. All coding exons, along with the exon-intron boundaries of GRM6, were sequenced bidirectionally.According to the medical history available to us, affected individuals in both families had experienced night blindness from the early years of their lives. Fundus photographs of affected individuals in both the families appeared normal, with no signs of attenuated arteries or bone spicule pigmentation. The scotopic electroretinogram (ERG) response were absent in all of the affected individuals, while the photopic measurements show reduced b-waves. During exclusion analyses, both families localized to a region on chromosome 5q that harbors GRM6, a gene previously associated with autosomal recessive CSNB. Bidirectional sequencing of GRM6 identified homozygous single base pair changes, specifically c.1336C>T (p.R446X) and c.2267G>A (p.G756D) in families PKRP170 and PKRP172, respectively.We identified a novel nonsense and a previously reported missense mutation in GRM6 that were responsible for autosomal recessive CSNB in patients of Pakistani decent.
| S-EPMC4636350 | biostudies-literature
Project description:PurposeTwo consanguineous Pakistani families with autosomal recessive primary congenital glaucoma were recruited to identify the disease locus.MethodsOphthalmic examinations including slit lamp biomicroscopy and applanation tonometry were employed to classify the phenotype. Blood samples were collected and genomic DNA was extracted. A genome wide scan was performed on both families with 382 polymorphic microsatellite markers. Two point LOD scores were calculated, and haplotypes were constructed to define the disease interval.ResultsClinical records and ophthalmic examinations suggest that affected individuals in families PKGL005 and PKGL025 have primary congenital glaucoma. Maximum two-point LOD scores of 5.88 with D14S61 at theta=0 and 6.19 with D14S43 at theta=0 were obtained for families PKGL005 and PKGL025, respectively. Haplotype analysis defined the disease locus as spanning a 6.56 cM (~4.2 Mb) genetic interval flanked by D14S289 proximally and D14S85 distally.ConclusionsLinkage analysis localizes autosomal recessive primary congenital glaucoma to chromosome 14q24.2-24.3 in consanguineous Pakistani families.
| S-EPMC2530517 | biostudies-literature
Project description:To identify the genetic origins of autosomal recessive congenital cataracts (arCC) in the Pakistani population.Based on the hypothesis that most arCC patients in consanguineous families in the Punjab areas of Pakistan should be homozygous for causative mutations, affected individuals were screened for homozygosity of nearby highly informative microsatellite markers and then screened for pathogenic mutations by DNA sequencing. A total of 83 unmapped consanguineous families were screened for mutations in 33 known candidate genes.Patients in 32 arCC families were homozygous for markers near at least 1 of the 33 known CC genes. Sequencing the included genes revealed homozygous cosegregating sequence changes in 10 families, 2 of which had the same variation. These included five missense, one nonsense, two frame shift, and one splice site mutations, eight of which were novel, in EPHA2, FOXE3, FYCO1, TDRD7, MIP, GALK1, and CRYBA4.The above results confirm the usefulness of homozygosity mapping for identifying genetic defects underlying autosomal recessive disorders in consanguineous families. In our ongoing study of arCC in Pakistan, including 83 arCC families that underwent homozygosity mapping, 3 mapped using genome-wide linkage analysis in unpublished data, and 30 previously reported families, mutations were detected in approximately 37.1% (43/116) of all families studied, suggesting that additional genes might be responsible in the remaining families. The most commonly mutated gene was FYCO1 (14%), followed by CRYBB3 (5.2%), GALK1 (3.5%), and EPHA2 (2.6%). This provides the first comprehensive description of the genetic architecture of arCC in the Pakistani population.
| S-EPMC5397132 | biostudies-literature
Project description:Glaucoma is the second leading cause of blindness, affecting ~65 million people worldwide. We identified and ascertained a large cohort of inbred families with multiple individuals manifesting cardinal symptoms of primary congenital glaucoma (PCG) to investigate the etiology of the disease at a molecular level. Ophthalmic examinations, including slit-lamp microscopy and applanation tonometry, were performed to characterize the causal phenotype and confirm that affected individuals fulfilled the diagnostic criteria for PCG. Subsequently, exclusion analysis was completed with fluorescently labeled short tandem repeat markers, followed by Sanger sequencing to identify pathogenic variants. Exclusion analysis suggested linkage to the CYP1B1 locus, with positive two-point logarithm of odds scores in 23 families, while Sanger sequencing identified a total of 11 variants, including two novel mutations, in 23 families. All mutations segregated with the disease phenotype in their respective families. These included the following seven missense mutations: p.Y81N, p.E229K, p.R368H, p.R390H, p.W434R, p.R444Q and p.R469W, as well as one nonsense mutation, p.Q37*, and three frameshift mutations, p.W246Lfs81*, p.T404Sfs30* and p.P442Qfs15*. In conclusion, we identified a total of 11 mutations, reconfirming the genetic heterogeneity of CYP1B1 in the pathogenesis of PCG. To the best of our knowledge, this is the largest study investigating the contribution of CYP1B1 to the pathogenesis of PCG in the Pakistani population.
| S-EPMC4972894 | biostudies-literature
Project description:To evaluate consanguineous pedigrees from Pakistan with a clinical diagnosis of nonsyndromic congenital retinal nonattachment (NCRNA) and identify genes responsible for the disease as currently only one NCRNA gene is known (atonal basic helix-loop-helix transcription factor 7: ATOH7).We implemented a three-step genotyping platform: single nucleotide polymorphism genotyping to identify loss of heterozygosity regions in patients, Retinal Information Network panel screening for mutations in currently known retinal genes. Negative patients were then subjected to whole exome sequencing.We evaluated 21 consanguineous NCRNA pedigrees and identified the causal mutations in known retinal genes in 13 out of our 21 families. We found mutations in ATOH7 in three families. Surprisingly, we then found mutations in familial exudative vitreoretinopathy (FEVR) genes; low-density lipoprotein receptor-related protein 5 mutations (six families), tetraspanin 12 mutations (two families), and NDP mutations (two families). Thus, 62% of the patients were successfully genotyped in our study with seven novel and six previously reported mutations in known retinal genes.Although the clinical diagnosis of all children was NCRNA with severe congenital fibrotic retinal detachments, the molecular diagnosis determined that the disease process was in fact a very severe form of FEVR in 10 families. Because severe congenital retinal detachment has not been previously associated with all the FEVR genes, we have thus expanded the phenotypic spectrum of FEVR, a highly variable retinal detachment phenotype that has clinical overlap with NCRNA. We identified seven novel mutations. We also established for the first time genetic overlap between the Iranian and Pakistani populations. We identified eight NCRNA families that do not harbor mutations in any known retinal genes, suggesting novel causal genes in these families.
| S-EPMC5308768 | biostudies-literature
Project description:In this study, hepatopancreas tissues of cold-tolerant and common families of Litopenaeus vannamei were selected by the Guangxi Academy of Fishery Sciences for proteomic study. Hepatopancreas were treated at 28℃, 18℃ and 10℃ respectively based on DIA technology. There were three replicates of cold-tolerant families and common families at 28℃, 18℃ and 10℃ respectively, and each replicate contained hepatopancreas mixed samples of 6 shrimp at random. A total of 18 samples were analyzed. The original data of common families at 28℃, 18℃ and 10℃ were named Lv-C-28、Lv-C-18 and Lv-C-10 respectively, while the original data of cold-tolerant families at 28℃, 18℃ and 10℃ were named Lv-T-28、Lv-T-18 and Lv-T-10 respectively.
2023-06-09 | PXD041965 |
Project description:BackgroundCongenital anomalies of the kidney and urinary tract (CAKUT) are the most prevalent cause of kidney disease in the first three decades of life. Previous gene panel studies showed monogenic causation in up to 12% of patients with CAKUT.MethodsWe applied whole-exome sequencing to analyze the genotypes of individuals from 232 families with CAKUT, evaluating for mutations in single genes known to cause human CAKUT and genes known to cause CAKUT in mice. In consanguineous or multiplex families, we additionally performed a search for novel monogenic causes of CAKUT.ResultsIn 29 families (13%), we detected a causative mutation in a known gene for isolated or syndromic CAKUT that sufficiently explained the patient's CAKUT phenotype. In three families (1%), we detected a mutation in a gene reported to cause a phenocopy of CAKUT. In 15 of 155 families with isolated CAKUT, we detected deleterious mutations in syndromic CAKUT genes. Our additional search for novel monogenic causes of CAKUT in consanguineous and multiplex families revealed a potential single, novel monogenic CAKUT gene in 19 of 232 families (8%).ConclusionsWe identified monogenic mutations in a known human CAKUT gene or CAKUT phenocopy gene as the cause of disease in 14% of the CAKUT families in this study. Whole-exome sequencing provides an etiologic diagnosis in a high fraction of patients with CAKUT and will provide a new basis for the mechanistic understanding of CAKUT.
| S-EPMC6115658 | biostudies-literature