"Like sugar in milk": reconstructing the genetic history of the Parsi population.

Background: The Parsis are one of the smallest religious communities in the world. To understand the population structure and demographic history of this group in detail, we analyzed Indian and Pakistani Parsi populations using high-resolution genetic variation data on autosomal and uniparental loci (Y-chromosomal and mitochondrial DNA). Additionally, we also assayed mitochondrial DNA polymorphisms among ancient Parsi DNA samples excavated from Sanjan, in present day Gujarat, the place of their original settlement in India.

The association of urinary interferon-gamma inducible protein-10 (IP10/CXCL10) levels with kidney allograft rejection.

Background: Interferon-gamma inducible protein-10 (IP-10/CXCL10) is a chemokine involved in the alloimmune response against kidney allograft. We aimed to investigate the association of urinary CXCL10 protein levels with rejection in renal transplant patients.

Methods: A total of 273 urine samples from (biopsy-proven) rejection and non-rejection patients and controls were included in this study.

Analysis of the glutathione S-transferase genes polymorphisms in the risk and prognosis of renal cell carcinomas. Case-control and meta-analysis.

Background: The Glutathione S-transferases (GSTs) genes deletion polymorphisms have been associated with the progression of several cancers. The association studies between the 2 GSTs (GSTM1 and GSTT1) null polymorphisms with the susceptibility to renal cell carcinoma (RCC) have been inconclusive. Therefore, with the inclusion of our own data, we performed a comprehensive meta-analysis to assess the association between these 2 polymorphisms and the risk of RCC.

Monoamine Oxidase A gene polymorphisms and self reported aggressive behaviour in a Pakistani ethnic group.

Objective: To investigate the association of monoamine oxidase Agene polymorphisms with aggression.

Methods: The study was conducted in an ethnic community in Lahore, Pakistan, from August 2008 to December 2009 on the basis of data that was collected through a questionnaire between August 2004 and September 2005. It analysed 10 single nucleotide polymorphisms of monoamine oxidase A in unrelated males from the same ethnic background who were administered a Punjabi translation of the Buss and Perry aggression questionnaire.

The Kalash genetic isolate: ancient divergence, drift, and selection.

The Kalash represent an enigmatic isolated population of Indo-European speakers who have been living for centuries in the Hindu Kush mountain ranges of present-day Pakistan. Previous Y chromosome and mitochondrial DNA markers provided no support for their claimed Greek descent following Alexander III of Macedon's invasion of this region, and analysis of autosomal loci provided evidence of a strong genetic bottleneck. To understand their origins and demography further, we genotyped 23 unrelated Kalash samples on the Illumina HumanOmni2.

Unique molecular alteration patterns in von Hippel-Lindau (VHL) gene in a cohort of sporadic renal cell carcinoma patients from Pakistan.

Background: Renal cell carcinoma (RCC) is the most frequent form of kidney cancer in adults. Somatic mutations that inactivate the von Hippel-Lindau (VHL) gene are the most common cause of RCC. The frequencies of molecular changes in the VHL gene in RCCs vary among different populations.

HLA class I and II polymorphisms in the Gujjar population from Pakistan.

HLA polymorphisms at the HLA -A, -B, -C, -DRB and -DQB1 loci were investigated in the Gujjar population from the Punjab province of Pakistan. The Gujjars (n = 97) were genotyped using sequence specific primers for polymerase chain reaction. The allele and haplotype frequencies were calculated and a neighbor-joining (NJ) tree comparing the Gujjar with other populations was constructed.

The effect of chemokine receptor gene polymorphisms (CCR2V64I, CCR5-59029G>A and CCR5Δ32) on renal allograft survival in Pakistani transplant patients.

Background: Gene polymorphisms of the chemokine receptors CCR2 and CCR5 (CCR2V64I, CCR5-59029G>A and CCR5Δ32) have been shown to be associated with renal allograft rejection. The aim of this study was to investigate the association of these polymorphisms with allograft rejection among Pakistani transplant patients.

Method: A total of 606 renal transplant patients and an equal number of their donors were included in this study.

A spectrum of novel NPHS1 and NPHS2 gene mutations in pediatric nephrotic syndrome patients from Pakistan.

Background: Mutations in the NPHS1 and NPHS2 genes are among the main causes of early-onset and familial steroid resistant nephrotic syndrome respectively. This study was carried out to assess the frequencies of mutations in these two genes in a cohort of Pakistani pediatric NS patients.

Methods: Mutation analysis was carried out by direct sequencing of the NPHS1 and NPHS2 genes in 145 nephrotic syndrome (NS) patients.

Polymorphisms in the methylene tetrahydrofolate reductase gene and their unique combinations are associated with an increased susceptibility to the renal cancers.

Aims: Two single nucleotide polymorphisms in the methylene tetrahydrofolate reductase (MTHFR) gene, 677C/T and 1298A/C, encode the thermolabile isoforms of the MTHFR enzyme that adversely affect the folic acid metabolic pathway. In the present study, these polymorphisms were investigated for their associations with the risk and prognosis of the renal cell carcinomas (RCCs) in Pakistani patients.

Results: The study included 168 RCC patients and 178 controls.

Association of the ACE-II genotype with the risk of nephrotic syndrome in Pakistani children.

Nephrotic syndrome is a common pediatric glomerular disease associated with heavy proteinuria. Since, the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism is a putative genetic risk factor for NS, in this study, ACE (I/D) polymorphism was analyzed in 268 NS and 223 control samples by a PCR-based method. The genotypic and allelic frequencies were determined and the association between ACE I/D polymorphism and NS was evaluated.

Association of a single-nucleotide polymorphism in the promoter region of the VEGF gene with the risk of renal cell carcinoma.

Aims: Vascular endothelial growth factor (VEGF) protein plays an important role in tumor development and progression. Polymorphisms in the VEGF gene may lead to over- or underexpression of the protein and may be associated with either risk or progression of malignancy. The aim of this case-control study is to identify and quantify the correlation between VEGF polymorphisms and renal cell carcinoma (RCC).

The distribution and most recent common ancestor of the 17q21 inversion in humans.

The polymorphic inversion on 17q21, sometimes called the microtubular associated protein tau (MAPT) inversion, is an approximately 900 kb inversion found primarily in Europeans and Southwest Asians. We have identified 21 SNPs that act as markers of the inverted, i.e.

Refined geographic distribution of the oriental ALDH2*504Lys (nee 487Lys) variant.

Mitochondrial aldehyde dehydrogenase (ALDH2) is one of the most important enzymes in human alcohol metabolism. The oriental ALDH2*504Lys variant functions as a dominant negative, greatly reducing activity in heterozygotes and abolishing activity in homozygotes. This allele is associated with serious disorders such as alcohol liver disease, late onset Alzheimer disease, colorectal cancer, and esophageal cancer, and is best known for protection against alcoholism.

Mapping of a novel type III variant of Knobloch syndrome (KNO3) to chromosome 17q11.2.

Knobloch syndrome (KNO) is an autosomal recessive disorder characterized by ocular abnormalities (myopia and retinal detachment) and occipital encephalocele. The syndrome is clinically and genetically heterogeneous (KNO1, KNO2). Previously germline mutations in COL18A1 (21q22.

Locus heterogeneity in autosomal recessive congenital cataracts: linkage to 9q and germline HSF4 mutations.

Isolated (non-syndromic) congenital cataract may be inherited as an autosomal dominant, autosomal recessive, or X-linked recessive trait. Considerable progress has been made in identifying genes and loci for dominantly inherited cataract, but the molecular basis for autosomal recessive disease is less well defined. Hence we undertook genetic linkage studies in four consanguineous Pakistani families with non-syndromic autosomal recessive congenital cataracts.