Sindhi Population Research Articles

Association of the Gene FTO Single Nucleotide Polymorphism, rs9939609 with Type 2 Diabetes Mellitus in Pakistani Cohort

To date, inconclusive data is available about the insight of the FTO gene variant with type 2 diabetes mellitus. T2DM is a chronic disease and a rising problem worldwide. Its complications lead to an increase in the burden of mortality specifically in lower and medium-income countries. Genome-wide association studies have spotted many genetic loci that are related to T2DM and validate the complicated polygenic traits. Many variants of different genes including FTO are associated with T2DM hence, this study was designed to inspect and unfold obscure data in South Asians. The main objective of present study is to identify the relation of FTO intronic variant rs9939609 with T2DM in Karachi-based Sindhi population of Pakistan. Total recruited individuals were grouped as diabetic cases and controls. Out of the total recruited subjects, genotyping was done on 152 samples using T-ARMS PCR however, demographic and clinical data were recorded of all individuals. The results showed that the frequency of variant genotypes in the diabetic case group was 11 % for AA, 45 % for AT and 44 % for TT though, the frequency of the lethal allele (T) was 34 %. These outcomes concluded, rare T allele frequency is higher among diabetic cases as compared to controls and provides the contribution from the Pakistani population to support the previous controversial findings. This study concluded FTO gene-single nucleotide polymorphism, rs9939609 is associated with T2DM but still, it is a growing need to do further studies on T2DM susceptible genes with different polymorphisms to recognize targets in the field of pharmacogenomics for clinical implementation.

Genetic diversity and forensic application of Y-filer STRs in four major ethnic groups of Pakistan

17 Y-chromosomal STRs which are part of the Yfiler Amplification Kit were investigated in 493 unrelated Pakistani individuals belonging to the Punjabi, Sindhi, Baloch, and Pathan ethnic groups. We have assessed the forensic parameters and population genetic structure for each group. Among the 493 unrelated individuals from four ethnic groups (128 Baloch, 122 Pathan, 108 Punjabi, and 135 Sindhi), 82 haplotypes were observed with haplotype diversity (HD) of 0.9906 in Baloch, 102 haplotypes with HD value of 0.9957 in Pathans, 80 haplotypes with HD value of 0.9924 in Punjabi, and 105 haplotypes with HD value of 0.9945 in the Sindhi population. The overall gene diversity for Baloch, Pathan, Punjabi, and Sindhi populations was 0.6367, 0.6479, 0.6657, and 0.6112, respectively. The results had shown us that Pakistani populations do not have a unique set of genes but share the genetic affinity with regional (Central Asia and Northern India) populations. The observed low gene diversity (heterozygosity) values may be because of endogamy trends and this observation is equally supported by the results of forensic parameters which are mostly static across 4 combinations (minimal STRs, extended 11 Y-STRs, Powerplex 12 Y System, and Yfiler 17 Y-STRs) of STRs in these four populations.

Machine-learning algorithm to non-invasively detect diabetes and pre-diabetes from electrocardiogram

ObjectivesEarly detection is of crucial importance for prevention of type 2 diabetes and pre-diabetes. Diagnosis of these conditions relies on the oral glucose tolerance test and haemoglobin A1c estimation which...

Susceptibility Loci for Type 2 Diabetes in the Ethnically Endogamous Indian Sindhi Population: A Pooled Blood Genome-Wide Association Study.

Type 2 diabetes (T2D) is a complex metabolic derangement that has a strong genetic basis. There is substantial population-specificity in the association of genetic variants with T2D. The Indian urban Sindhi population is at a high risk of T2D. The genetic basis of T2D in this population is unknown. We interrogated 28 pooled whole blood genomes of 1402 participants from the Diabetes In Sindhi Families In Nagpur (DISFIN) study using Illumina’s Global Screening Array. From a total of 608,550 biallelic variants, 140 were significantly associated with T2D after adjusting for comorbidities, batch effects, pooling error, kinship status and pooling variation in a random effects multivariable logistic regression framework. Of the 102 well-characterized genes that these variants mapped onto, 70 genes have been previously reported to be associated with T2D to varying degrees with known functional relevance. Excluding open reading frames, intergenic non-coding elements and pseudogenes, our study identified 22 novel candidate genes in the Sindhi population studied. Our study thus points to the potential, interesting candidate genes associated with T2D in an ethnically endogamous population. These candidate genes need to be fully investigated in future studies.

Polymorphisms in CYP2C8 Gene in Pakistani Population and Their Frequencies in Various Ethnic Groups

Cytochrome P4502C8 represents 7% of the hepatic cytochrome system and metabolizes around 5% of drugs in phase I processes. It also plays a significant role in the metabolism of endogenous compounds. More than 20 single nucleotide polymorphisms (SNPs) have been reported, mainly in exon 3, 5, and 8. Some of the SNP’s lead to decreased enzyme activity and may have impact on drug metabolism. This research study aims to determine the frequencies of the most common SNPs of the CYP2C8 gene (CYP2C8*2, *3, *4) in the Pakistani population. A cross-sectional study consisting of 391 healthy humans was conducted after taking informed consent. DNA was extracted using commercial kits, and allelic and genotype frequencies were determined after PCR amplification, restriction fragment length polymorphism, and gel electrophoresis. The rate of minor allele was found to be 11.64% for CYP2C8*2, 14.71% for CYP2C8*3, and 1.53% for CYP2C8*4. Comparison with the 1000 Genome project reveals that the allelic frequencies of CYP2C8*4 in Pakistani population were similar to other South Asian populations while the frequencies of CYP2C8*2 and CYP2C8*3 as significantly different from other South Asian populations. A significant interethnic variation was also observed among Pakistani ethnicities. The CYP2C8*2 allele was highest in the Sindhi population, CYP2C8*3 in the Pashtoon population and CYP2C8*4 in the Balochi population. These data suggest that the frequency of poor metabolizers of CYP2C8 is high enough in the Pakistani population to warrant further genotype-phenotype correlations studies on individual drugs metabolized by CYP2C8 enzyme.

Anthropological analyses of 30 insertion/deletion autosomal markers in five major ethnic groups of Pakistan

We investigated the forensic efficacy of the 30 insertion/deletion (Indel) markers included in the Qiagen Investigator® DIPplex kit in 529 Pakistani individuals from five major subpopulations in Pakistan (Punjabi, Pashtun, Sindhi, Saraiki, and Baloch). In the Sindhi population, the distribution of HLD81 and HLD97 alleles deviated from Hardy-Weinberg equilibrium after Bonferroni correction. The combined match probability ranged from 2.0E-12 (Pashtun and Baloch) to 1.0E-12 (Sindhi), and the mean paternity exclusion power varied from 0.995 (Punjabi, Sindhi, and Saraiki) to 0.996 (Pashtun and Baloch). The high combined power of discrimination (0.999 999 999 999 97) and low combined match probability (1.7E-12) for all subpopulations studied support the utility of the 30 Indel markers for forensic identification in the studied subpopulations. The allele frequencies of the Indel markers in the Pakistani subpopulations were compared with those from 18 other populations. The results show that the populations clustered according to geography. The subpopulations investigated in this work showed a close genetic relationship with others from Pakistan, as well as with South Central Asian and Middle Eastern populations. The results suggest that the Investigator® DIPplex kit can be useful as a supplementary tool for human identification in the five Pakistani subpopulations investigated in this study. Supplemental data for this article is available online at https://doi.org/10.1080/20961790.2021.1933366 .

Forensic Genetic Analysis of 11 Rapidly Mutating Y-STRs (RM-YSTRs) in Sindhi Population of Pakistan

Forensic Science is robustly associated with DNA that has a complex genetic blue print information intended to resolve the queries related to civil cases, judiciary, investigatory purposes and crime scenes. The study was carried out to contribute the data set of RMYSTRs (Rapidly Mutating YSTRs) globally. The study focused on the significance of using RM-YSTRs as compared to the set of 9-17 YSTRs (mutation rate 1 × 10-2), as the later one is not being able to attain a high magnitude of male relatives differentiation. In the present work, 100 Sindh DNA male samples were collected, by genotyping the amplified samples, using RM-YSTRs, having a mutation rate of 1 × 10-3. Forensic efficiency parameters such as, PIC (Polymorphism Information Content) was observed in the range of 0.7745 at locus DYS576 to 0.9313 at locus DYF399S1b, maximum gene diversity (0.9350) was found at locus DYF399S1b, minimum gene diversity (0.7978) was seen at locus DYS576. Highest value of allele frequency was found as 0.350 with the allele no 18 at locus DYS576. The results had shown that haplotype frequency and haplotype diversity value were 0.010 and 0.99297, as no haplotype was repeated, which highlighted on the fact that nearly complete male individualization can be obtainedusing RM YSTRs, thus helpful in avoiding the adventitious matches or exclusion or inclusion of male relatives in forensics cases work. It might be an initiative towards establishing RM YSTR database of Pakistani Sindhi population.

Identification of a new Indian camel germplasm by microsatellite markers based genetic diversity and population structure of three camel populations.

Camel invokes fascinating chapter of Indian desert history and is integral component of its ecosystem. Camel population has reached a crisis point after three decades of decline (75%) causing major concern to the policy makers. >28% of Indian camel is not yet characterized. It is imperative to describe country’s camel germplasm and its existing diversity for designing conservation plan. One such population is Sindhi, distributed along border with Pakistan. Twenty five microsatellite markers being valuable tool for estimating genetic diversity were selected to elucidate genetic variability and relationship of Sindhi with two registered camel breeds of India- Marwari and Kharai. The standard metrics of genomic diversity detected moderate variability in all the three populations. A total of 303 alleles with a mean of 8.116 ± 0.587 alleles per locus were found in total of 143 animals. Sindhi population had intermediate allelic diversity with 8.522 ± 1.063 alleles per locus. Corresponding values in Marwari and Kharai were 8.783 ± 0.962 and 7.043 ± 1.030, respectively. Genetic variability within the breeds was moderate as evidenced by the mean observed heterozygosity of 0.556 ± 0.025. Sindhi camel population harbors higher genetic variability (Ho = 0.594) as compared to the two registered camel breeds (Marwari, 0.543 and Kharai, 0.531). Mean expected heterozygosity under Hardy-Weinberg equilibrium was higher than the observed values across the three camel groups, indicating deviations from assumptions of this model. In fact, average positive F value of 0.084 to 0.206 reflected heterozygote deficiency in these populations. These Indian camel populations have not experienced serious demographic bottlenecks in the recent past. Differences among populations were medium and accounted for 7.3% of total genetic variability. Distinctness of three camel populations was supported by all the approaches utilized to study genetic relationships such as genetic distances, phylogenetic relationship, correspondence analysis, clustering method based on Bayesian approach and individual assignment. Sindhi camel population was clearly separated from two registered breeds of Indian camel. Results conclude Sindhi to be a separate genepool. Moderate genetic diversity provides an optimistic viewpoint for the survival of severely declining indigenous camel populations with appropriate planning strategies for conserving the existing genetic variation and to avoid any escalation of inbreeding.

Systematic sequence analysis of the FUT3 gene identifies 11 novel alleles in the Sindhi and Punjabi populations from Pakistan

The FUT3 (Lewis) gene is responsible for the expression of Lewis fucosyltransferase, which is required for the synthesis of the structural determinants of both Lewisa and Lewisb specificity. These factors play an important role not only in clinical but also in medico-legal investigations. The gene sequence is highly polymorphic and ethnically specific. In the current study, we performed systematic sequence analysis of the coding region of FUT3 by DNA sequencing to investigate the genetic variations of FUT3 and the molecular basis of the Lewis phenotype in the Sindhi and Punjabi populations of Pakistan. Twenty-three point mutations were observed, including 7 unreported mutations, among which two missense mutations (490 G > A and 959 T > C) were predicted to be deleterious to enzyme activity by software assessment. In total, we observed 24 Lewis alleles, including 11 novel ones. However, all unreported missense mutations were present in Lewis-negative alleles confirmed previously. According to genotypic data, the Lewis-negative phenotypic frequencies were 11.5% and 22.93% in the Sindhi and Punjabi ethnic groups, respectively. Moreover, we found that le202,314 and le59,1067 were predominant among Lewis-negative alleles, while the frequency of le59,1067 in the Punjabi population was significantly higher than that in the Sindhi population. In summary, our study revealed that there is a relatively high degree of sequence variation of the Lewis gene in Pakistani populations and provided the first genetic data on FUT3 in these two ethnic groups from Pakistan. The allele types and their frequencies showed that these ethnic groups exhibit more Caucasian components.

Genetic characterization of 15 autosomal STRs in the interior Sindhi population of Pakistan and their phylogenetic relationship with other populations.

Genetic structure of a population can be influenced by evolutionary processes and cultural histories which can alter the frequencies of different variants at particular genetic markers. These characteristics make DNA evidence suitable for forensic applications. Little relevant data are available from the interior Sindhi population; thus, in the current study, we have investigated 15 autosomal STRs in 181 unrelated individuals belonging to the interior parts of Sindh Pakistan, to establish its lineage and parameters of forensic interest. These STRs revealed a high power of discrimination (CPD), power of exclusion (CPE) and matching probability (CMP) are 0.9999999999999999968997, 0.99998612 and 3.1003×10-18 respectively. The genetic distances, neighbour-joining (NJ) tree, interactivity test and principal component analysis (PCA) based on 15 autosomal STR loci showed that the interior Sindhi population had a closer genetic relationship with Pakistani populations and distant relationships with regional (India and Afghanistan) populations. The present findings exhibited that STRs included in AmpFLSTR Identifiler kit (Applied Biosystems) are genetically polymorphic in the interior Sindhi population of Pakistan. This study provides valuable population genetic data for the genetic information study, forensic human individual identification and paternity testing.

Parentage assignment using SNP markers, inbreeding and population size for the Brazilian Red Sindhi cattle

Brazilian Red Sindhi was originated from a very small number of founders and showed a consistent growth during the last three decades. One relevant herd was kept without proper birth recording and the reconstruction of parentage was possible for this herd through the use of a panel with 3894 SNP markers. Pedigree errors were also identified and corrected for animals sampled in various herds distributed in different Brazilian regions. A panel containing 71 SNP markers was indicated as the minimum number for the effective parentage verification within the Red Sindhi population in Brazil. Corrected genealogy was used for the description of inbreeding and effective population size, which was accessed with the paired increases in coancestry approach. Average inbreeding was high (F = 9.03%) for 15,217 inbred animals (54.1% of the total). Nevertheless, a trend of decrease with time was observed for this parameter with the average individual increases in inbreeding approach (∆Fi). This population went through a bottleneck during the 1980s and beginning of the 1990s, reaching a minimum population size of Ne=55.86. After that period, a consistent increase in the number of breeders and animals has raised the effective population size to the current value of Ne=87.55.

Genetic variations of 15 autosomal and 17 Y-STR markers in Sindhi population of Pakistan.

This study comprises genetic characterization of 15 autosomal and 17 Y-chromosomal STR loci in 103 unrelated male inhabitants of the Sindhi population to establish its lineage and parameters of forensic interest. The examined autosomal STRs revealed high combined power of discrimination, combined power of exclusion, and the combined matching probability as 0.99999999999999999042580, 0.9999977141, and 9.5742×10-18, respectively. A total of 89 unique haplotypes were obtained, of which 84 were observed once with a haplotype diversity value of 0.999677. The resulted Y-STR haplotypes exhibited a high degree of geographical demarcation by comparing with other populations at the local and global levels.

Incidence of Sickle Cell Anaemia and Thalassaemia in Central India

Haemoglobinopathies are group of diseases characterized by abnormalities both quantitative and qualitative in the synthesis of haemoglobin. Haemoglobinopathies consist of sickle cell anaemia (SCA), thalassaemia (βT) and variant haemoglobins. In India, they are responsible for the largest number of genetic disorders and hence are of great public health hazardous. In India major concerned haemoglobinopathic disorders are sickle cell anaemia and β-thalassaemia. Of the several abnormal haemoglobin molecules, four which are widely prevalent in India include: HbS, HbβT, HbE and HbD. Examination of 6463 individuals showed high incidences for haemoglobin variants, HbS and HbβT in different ethnic groups, the frequency being varies from 0% - 20% and 0% - 9% respectively. The frequency of HbS in Brahmins is 4.17%, in Kalar 5.41%, in Rajput 2.04%, in Muslims 3.73% in Maratha 2.08% in Bania 9.09% while in Teli it is 3.65%. Among the Scheduled castes and Nomadic tribal groups HbS ranges from 1% - 12%; in backward caste categories it varies from 3% - 16%; while in Scheduled tribes it ranges from 0% - 20%. The high magnitude of sickle cell trait has been noticed in the Pardhan (20.31%) followed by the Marar (16.10%), the Dhiwar (11.90%), the Gond (11.89%), the Mahar (11.81%) and the Bania (9.90%). A considerable high frequency (9.27%) of β-thalassaemia has been observed among the Sindhi population. Sporadic occurrence of HbβT and HbD among other communities suggested the gradual spread of the genes into the region. The present findings in 11 communities with the thalassaemia syndrome suggest that the β-thalassaemia is accompanied by raised level of HbA2. Unusual greater mean RBC and WBC suggest the high concentration of hypochromic microcytosis in anaemia. The mean MCV and MCH in HbβT and HbD are much lower than the normal ranges compared to HbS. The mean MCHC is much lower in HbβT, HbDD and HbS than the normal range. The cumulative gene frequency of haemoglobinopathies in India is 4.2%. With a population of over 1 billion and a birth rate of 28 per 1000, there are over 42 million carriers and over 12,000 infants are born each year with a major and clinical significant haemoglobinopathy. Out of these, clinically significant sickle cell anaemia and β-thalassaemic disorders account for almost equal numbers.

Prevalence of β-thalassaemia in subcastes of Indian Sindhis: Results from a two-phase survey

To estimate the prevalence of beta-thalassaemia in different subcastes of the Indian Sindhi population who, in general, have a high prevalence of this disease. A two-phase, community-based survey. Asymptomatic, Sindhi volunteers from Nagpur, central India, were recruited into the present study over a 7-year period. The first phase included the use of the Naked Eye Single Tube Red cell Osmotic Fragility Test (NESTROFT). Those positive for NESTROFT or those volunteering for haemoglobin A(2) (HbA(2)) quantification entered the second phase of the survey. Appropriate statistical methods for estimating prevalence from two-phase surveys were used. The prevalence of beta-thalassaemia carriers across the five major Sindhi subcastes varied substantially in the study population. Larkana Sindhis had the highest (17%) whereas Dadu Sindhis had the lowest (8%) frequency of the beta-thalassaemia allele. As a corollary, the projected incidence of beta-thalassaemia major in newborn babies greatly varied by the subcastes of the parents. Ethnic subgroups within populations known to commonly carry the beta-thalassaemia gene provide further information that is useful from epidemiological and public health perspectives.

Incidence of xeroderma pigmentosum in Larkana, Pakistan: a 7-year study

Xeroderma pigmentosum (XP) is a rare autosomal recessive inherited disorder caused by a defect in the normal repair of DNA of various cutaneous cell types damaged by exposure to ultraviolet radiation. We present our 7-year experience with 36 XP patients who either visited the Department of Dermatology or were seen in the medical camps arranged in remote areas for patients' welfare, from 1995 to 2001. For ease of discussion we classified all cases into the following subgroups on clinical grounds only: mild, those with light brown freckles on the face alone; moderate, those with dark brown freckles with burning on the face, neck, ears, chest, hands and photophobia but without other associated obvious cutaneous and ocular changes; severe, those with extensive dark brown freckles with burning on the exposed parts as well as on the unexposed parts of the body, i.e. the chest, back, abdomen and arms including other associated cutaneous and ocular changes such as ulcers and malignancy. Of 36 patients, three (8.3%) were classified as mild, nine (25%) moderate and 24 (66.7%) severe; there were 18 males and 18 females, age range 2-30 years (mean 8.9 years). Seventeen patients had cutaneous changes: actinic keratosis, keratoacanthoma, fissures and ulcerative nodules on the exposed parts of the body. Four patients had wide ulcers, along with mass formation and severe pigmentation on the face, neck and head. Twenty-nine patients developed ocular symptoms: photophobia, conjunctivitis, corneal keratitis and lid ulcer. One patient had complete loss of vision. Histopathological findings revealed that six patients had squamous cell carcinoma (SCC) on the face, head, ear or lip. More than one sibling (two to four) was affected in four families. The majority of cases (20/36, 55.6%) were from the Brohi tribe (skin type III), while the remaining cases (16/36, 44.4%) were from the Sindhi population (skin type IV). The large number of XP patients seen in those with skin type III (Brohi tribe) compared with skin type IV (Sindhi population) indicates that the skin type and the race has a considerable value in the pathogenesis of XP. Furthermore, 24 of 36 patients were in the severe group and six of these had SCC. Moreover, no neurological abnormalities were observed in our patients. All patients were treated according to disease severity by prescribing oral antibiotics, local steroids, sunscreens and/or chemotherapy followed by irradiation in malignant cases. Two patients died because of extensive SCC.

HLA-A, -B, -Cw, -DQB1 and -DRB1 allele frequencies in a Sindhi population from Pakistan

HLA-A, -B, -Cw, -DQB1 and -DRB1 allele frequencies in a Sindhi population from Pakistan

ABO and Rh Blood Groups Among Sindhis of Jabalpur, Madhya Pradesh

The present paper reports the distribution of the ABO and Rh blood groups among the Sindhi population of Jabalpur. Allele frequency of A is observed quite low (8. 33%). The frequency of Rh negative...