| 1. |
- Nawaz, Sadia, et al.
(författare)
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Report of a recurrent mutation in ARS (component B) gene with severe Mal de Meleda in a large consanguineous Pakistani family
- 2011
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Ingår i: Pakistan journal of medical sciences print. - 1682-024X .- 1681-715X. ; 27:3, s. 686-689
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To characterize the disease causing mutation in a large consanguineous Pakistani family with severe Mat de Meleda (MDM) or keratosis palmoplantaris transgrediens, a rare autosomal recessive skin disorder. Methodology: Single nucleotide polymorphism (SNPs) genotyping was performed using the Gene Chip Mapping 250K array (Affymetrix). Homozygosity mapping and sorting of genomic regions were performed with dedicated software called AutoSNPa. Selected regions were further investigated by genotyping with microsatellite markers derived from known and novel pOlymorphic repeats. Two-point LOD score calculation was performed by using the MLINK of Fast link computer package. All three coding exons of ARS (component B) gene were amplified by PCR and sequenced. Conclusion: Sequencing of all the coding exons of ARS (component B) gene in the affected individuals revealed a recurrent missense mutation in exon 3 at base pair 256 from Guanine to Alanine (256G>A) and as a result the amino acid Glycine is replaced by Arginine at position 86 (G86R). This finding will facilitate control of affected MDM births in the Pakistani families.
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| 2. |
- Raykova, Doroteya, et al.
(författare)
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Autosomal Recessive Transmission of a Rare KRT74 Variant Causes Hair and Nail Ectodermal Dysplasia : Allelism with Dominant Woolly Hair/Hypotrichosis
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:4, s. e93607-
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Tidskriftsartikel (refereegranskat)abstract
- Pure hair and nail ectodermal dysplasia (PHNED) comprises a heterogeneous group of rare heritable disorders characterized by brittle hair, hypotrichosis, onychodystrophy and micronychia. Autosomal recessive (AR) PHNED has previously been associated with mutations in either KRT85 or HOXC13 on chromosome 12p11.1-q14.3. We investigated a consanguineous Pakistani family with AR PHNED linked to the keratin gene cluster on 12p11.1 but without detectable mutations in KRT85 and HOXC13. Whole exome sequencing of affected individuals revealed homozygosity for a rare c.821T> C variant (p.Phe274Ser) in the KRT74 gene that segregates AR PHNED in the family. The transition alters the highly conserved Phe274 residue in the coil 1B domain required for long-range dimerization of keratins, suggesting that the mutation compromises the stability of intermediate filaments. Immunohistochemical (IHC) analyses confirmed a strong keratin-74 expression in the nail matrix, the nail bed and the hyponychium of mouse distal digits, as well as in normal human hair follicles. Furthermore, hair follicles and epidermis of an affected family member stained negative for Keratin-74 suggesting a loss of function mechanism mediated by the Phe274Ser substitution. Our observations show for the first time that homozygosity for a KRT74 missense variant may be associated with AR PHNED. Heterozygous KRT74 mutations have previously been associated with autosomal dominant woolly hair/ hypotrichosis simplex (ADWH). Thus, our findings expand the phenotypic spectrum associated with KRT74 mutations and imply that a subtype of AR PHNED is allelic with ADWH.
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| 3. |
- Tanveer, M. K., et al.
(författare)
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Prevalence and chemo-therapeutical investigations of gastrointestinal nematodes in domestic pigeons in Lahore, Pakistan
- 2011
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Ingår i: Tropical Biomedicine. - 0127-5720. ; 28:1, s. 102-110
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of gastrointestinal nematodes was studied in 143 (80 male and 63 female) domestic pigeons. Faecal samples were collected to determine the gastrointestinal nematodes of domestic pigeons through qualitative and quantitative faecal examinations. A total of 48 (male 33 and 25 female) naturally infected domestic pigeons were divided into G(1) (albendzdole) and G(2) (fenbendazole) treatment-groups along with one control group (C). The overall prevalence of gastrointestinal nematodes was 40.5% (58/143) in domestic pigeons. Likewise, the prevalence of gastrointestinal nematodes in males and females was found 41.3% (33/58) and 39.7% (25/58) respectively. The overall prevalence of Capillaria obsignata and Ascaridia columbae was found to be 67.2% and 32.8%, respectively. The prevalence of C. obsignata and A. columbae in males was 72.7% (24/33) and 27.8% (9/33) and in females was 60% (15/25) and 40% (10/25), respectively. There was no significant sex related difference seen in the prevalence of C. obsignata (p>0.56) and A. columbae (p>0.40) in domestic pigeons, respectively. The overall efficacy of albendazole and fenbendazole was calculated to be 66% and 71%. A remarkable significant difference (p<0.05) was observed in eggs per gram before and after treatment in both G(1) and G(2) treated-groups. The efficacy of fenbendazole was found to be more significant (p<0.02) than albendazole.
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| 4. |
- Azhar, Aysha, et al.
(författare)
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A novel mutation in Lysophosphatidic Acid Receptor 6 gene in autosomal recessive hypotrichosis and evidence for a founder effect
- 2012
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Ingår i: EJD. European journal of dermatology. - : John Libbey Eurotext. - 1167-1122 .- 1952-4013. ; 22:4, s. 464-466
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in the lysophosphatidic acid receptor 6 (LPAR6) gene cause localized autosomal recessive hypotrichosis. We report six consanguineous families from Pakistan with segregating hypotrichosis localized to the scalp. Genetic investigation using polymorphic microsatellite markers revealed homozygosity spanning the LAH3 locus on chromosome 13 in affected individuals of all six families. Sequence analysis of the LPAR6 gene showed a novel insertion resulting in a frameshift and a premature termination (p.I194FfsX11) in affected members of one family. In the remaining five families we identified a previously described missense mutation (p.G146R) in a homozygous state in affected members. The closest flanking polymorphic marker showed an identical allele size in the five families segregating with the p. G146R mutation, supporting a single origin of this variation. These findings extend the spectrum of known LPAR6 mutations and suggest a founder effect of the p. G146R mutation in the Pakistani population.
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| 5. |
- Azhar, Muhammad Waqar, 1986, et al.
(författare)
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Cyclic Redundancy Checking (CRC) Accelerator for the FlexCore Processor
- 2010
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Ingår i: Proceedings of Euromicro Conference on Digital System Design (DSD). - 9780769541716 ; , s. 675-680
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Konferensbidrag (refereegranskat)abstract
- A proven approach to increase performance of general-purpose processors is to add hardware accelerators. In its basic configuration, the FlexCore processor has a limited set of datapath units. But thanks to a flexible datapath interconnect and a wide control word, the FlexCore datapath is explicitly designed to support integration of special units that, on demand, can accelerate certain data-intensive applications. We present the integration of a versatile accelerator for several Cyclic Redundancy Checking (CRC) keys. Furthermore, we investigate the accelerator's impact on processor execution time and energy efficiency, using the PowerStone CRC benchmark. Our evaluation shows that the accelerated 65-nm 2.7-ns FlexCore datapath is, for example, 86% more energy and cycle efficient than a datapath lacking the CRC accelerator. © 2010 IEEE.
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| 6. |
- Azhar, Muhammad Waqar, 1986, et al.
(författare)
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Viterbi Accelerator for Embedded Processor Datapaths
- 2012
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Ingår i: Proceedings of the International Conference on Application-Specific Systems, Architectures and Processors. - 1063-6862. - 9780769547688 ; , s. 133-140
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Konferensbidrag (refereegranskat)abstract
- We present a novel architecture for a lightweight Viterbi accelerator that can be tightly integrated inside an embedded processor. We investigate the accelerator’s impact on processor performance by using the EEMBC Viterbi benchmark and the in-house Viterbi Branch Metric kernel. Our evaluation based on the EEMBC benchmark shows that an accelerated 65-nm 2.7-ns processor datapath is 20% larger but 90% more cycle efficient than a datapath lacking the Viterbi accelerator, leading to an 87% overall energy reduction and a data throughput of 3.52 Mbit/s.
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| 7. |
- Peden, John F., et al.
(författare)
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A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:4, s. 339-344
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have identified 11 common variants convincingly associated with coronary artery disease (CAD)(1-7), a modest number considering the apparent heritability of CAD(8). All of these variants have been discovered in European populations. We report a meta-analysis of four large genome-wide association studies of CAD, with similar to 575,000 genotyped SNPs in a discovery dataset comprising 15,420 individuals with CAD (cases) (8,424 Europeans and 6,996 South Asians) and 15,062 controls. There was little evidence for ancestry-specific associations, supporting the use of combined analyses. Replication in an independent sample of 21,408 cases and 19,185 controls identified five loci newly associated with CAD (P < 5 x 10(-8) in the combined discovery and replication analysis): LIPA on 10q23, PDGFD on 11q22, ADAMTS7-MORF4L1 on 15q25, a gene rich locus on 7q22 and KIAA1462 on 10p11. The CAD-associated SNP in the PDGFD locus showed tissue-specific cis expression quantitative trait locus effects. These findings implicate new pathways for CAD susceptibility.
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| 8. |
- Rasool, Mahmood, et al.
(författare)
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Autosomal recessive pure hair and nail ectodermal dysplasia linked to chromosome 12p11.1-q14.3 without KRTHB5 gene mutation
- 2010
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Ingår i: EJD. European journal of dermatology. - : John Libbey Eurotext. - 1167-1122 .- 1952-4013. ; 20:4, s. 443-446
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Tidskriftsartikel (refereegranskat)abstract
- Hair-nail ectodermal dysplasia (HNED; OMIM 602032) constitutes a rare subgroup of ectodermal dysplasias characterised by onychodystrophy, hypotrichosis and brittle hair. We identified a large consanguineous Pakistani family with four siblings affected by a congenital autosomal recessive form of the disease. Based on previous genetic findings in HNED we performed linkage analysis in the family using chromosome 12 markers. A genetic linkage analysis revealed a lod score of 2.92 ( = 0.0) at locus D12S368, indicating the disease gene to be located on chromosome 12. Candidate genes on chromosome 12, including the KRTHB5 gene and four additional keratin II genes, were sequenced in affected family members. Sequence analysis of the coding regions of keratin KRTHB5 gene, previously associated with a distinct clinical form of hair-nail dysplasia, revealed normal coding regions. Our study confirms linkage of a variant clinical form of hair-nail ectodermal dysplasia to chromosome 12 without any mutation in the coding sequences of the KRTHB5 gene. The results suggest this family to have either a non-coding mutation in the KRTHB5 gene, or a mutation in a yet unknown gene within the linked region on chromosome 12.
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