Increased Rate of Deleterious Variants in Long Runs of Homozygosity of an Inbred Population from Qatar
Conclusion: Genes located within ROH hotspot regions contain a significant burden of predicted putatively deleterious variants compared to genes located outside these regions, suggesting inbreeding as a possible mechanism allowing an enrichment of putatively deleterious variants at the homozygous state.Hum Hered 2015;79:14-19 (Source: Human Heredity)
Source: Human Heredity - February 20, 2015 Category: Genetics & Stem Cells Source Type: research
Contents Vol. 78, 2014
Hum Hered 2014;78:I-III (Source: Human Heredity)
Source: Human Heredity - February 13, 2015 Category: Genetics & Stem Cells Source Type: research
The Missing Heritability Paradigm: A Dramatic Resurgence of the GIGO Syndrome in Genetics
Hum Hered 2015;79:10-13 (Source: Human Heredity)
Source: Human Heredity - February 6, 2015 Category: Genetics & Stem Cells Source Type: research
Prioritizing Rare Variants with Conditional Likelihood Ratios
Conclusion: The maxLRc provides reliable statistical prioritization of rare variants using only the observed data, avoiding the need to specify parameters associated with hypothesis testing that can result in ranking discrepancies across p value procedures; and it is applicable to common variant prioritization.Hum Hered 2015;79:1-9 (Source: Human Heredity)
Source: Human Heredity - February 2, 2015 Category: Genetics & Stem Cells Source Type: research
Fast Linkage Analysis with MOD Scores Using Algebraic Calculation
Conclusion: Computation times for MOD-score analysis, involving the evaluation of many tested sets of trait-model parameters and p value calculation, have been prohibitively high so far. With our new algebraic algorithm, such an analysis is now feasible within a reasonable amount of time.Hum Hered 2014;78:179-194 (Source: Human Heredity)
Source: Human Heredity - January 29, 2015 Category: Genetics & Stem Cells Source Type: research
A Community-Based Study of Mucopolysaccharidosis Type VI in Brazil: The Influence of Founder Effect, Endogamy and Consanguinity
Mucopolysaccharidosis type VI (MPS VI - Maroteaux-Lamy syndrome) is a globally rare lysosomal storage disease caused by a deficiency of arylsulfatase B. However, in Monte Santo, a poor and isolated rural region in Northeast Brazil with large family sizes and high rates of community endogamy and parental consanguinity (α = 0.00483), 9 living and 4 now deceased individuals in 11 kindreds have been diagnosed with MPS VI, all with the same p.H178L missense founder mutation. A further 33 deceased persons have been identified by family members as exhibiting the disease phenotype. Detailed pedigrees were constructed for the 13 g...
Source: Human Heredity - January 18, 2015 Category: Genetics & Stem Cells Source Type: research
The Use of Autozygosity Mapping and Next-Generation Sequencing in Understanding Anterior Segment Defects Caused by an Abnormal Development of the Lens
The formation of the anterior segment of the eye is an intricate process that is dependent to a large degree on the normal development of the lens. Despite intensive study of the role of well-described eye genes, many causes of lenticular and anterior segment anomalies remain elusive. The majority of genes implicated thus far act in an autosomal dominant manner. Autosomal recessive causes are less well described; their diagnosis has been hindered by technological limitations, extreme genetic heterogeneity, a lack of understanding of eye biology and the role of many genes within the genome. The opportunity for the discovery...
Source: Human Heredity - January 18, 2015 Category: Genetics & Stem Cells Source Type: research
Rare Variant Testing of Imputed Data: An Analysis Pipeline Typified
Important methodological advancements in rare variant association testing have been made recently, among them collapsing tests, kernel methods and the variable threshold (VT) technique. Typically, rare variants from a region of interest are tested for association as a group (‘bin'). Rare variant studies are already routinely performed as whole-exome sequencing studies. As an alternative approach, we propose a pipeline for rare variant analysis of imputed data and develop respective quality control criteria. We provide suggestions for the choice and construction of analysis bins in whole-genome application and support the...
Source: Human Heredity - December 10, 2014 Category: Genetics & Stem Cells Source Type: research
Consanguinity and Hereditary Hearing Loss in Qatar
Qatar is a sovereign state located on the Eastern coast of the Arabian Peninsula in the Persian Gulf. Its native population consists of 3 major subgroups: people of Arabian origin or Bedouins, those from an Eastern or Persian ancestry and individuals with African admixture. Historically, all types of consanguineous marriages have been and still are common in the Qatari population, particularly among first and double-first cousins. Thus, there is a higher risk for most inherited diseases including hereditary hearing loss (HHL). In particular, a hearing loss prevalence of 5.2% has been reported in Qatar, with parental consan...
Source: Human Heredity - November 14, 2014 Category: Genetics & Stem Cells Source Type: research
Consanguinity, Endogamy and Inborn Errors of Metabolism in Oman: A Cross-Sectional Study
The Sultanate of Oman, like many other Arab countries, has relatively high rates of consanguinity. Reports suggest that the incidence of inborn errors of metabolism (IEM) is also high in Oman. This retrospective cross-sectional study was designed to evaluate the number of patients with IEM being followed at the only two tertiary centers in Oman treating such patients, and to calculate the consanguinity rates among these families. The electronic medical records of all patients were reviewed for demographic and clinical characteristics. A total of 285 patients with IEM were being followed at the 2 centers involved; 162 (56.8...
Source: Human Heredity - November 14, 2014 Category: Genetics & Stem Cells Source Type: research
Consanguineous Marriage, Reproductive Behaviour and Postnatal Mortality in Contemporary Iran
Conclusions: Given declining family sizes, a rapid urbanization and increased educational and employment opportunities, it seems inevitable that consanguineous marriages will decline in prevalence in Iran, albeit more slowly in more traditional rural communities. Predictably, there will be a concomitant reduction in the incidence of recessive genetic disorders, but this is against a background transition from communicable to non-communicable diseases.Hum Hered 2014;77:16-25 (Source: Human Heredity)
Source: Human Heredity - November 14, 2014 Category: Genetics & Stem Cells Source Type: research
Consanguinity and Prevalence Patterns of Inherited Disease in the UK Pakistani Community
Conclusions: The analysis suggests that much of the increased mortality and morbidity in UK Pakistani children is due to autosomal recessive conditions. Evidence suggests that this finding is associated with the custom of consanguineous marriage, but future studies might also explore the role of community endogamy. Prevalence data from the first and second post-migration generations could additionally be useful in informing health planning in Pakistan.Hum Hered 2014;77:207-216 (Source: Human Heredity)
Source: Human Heredity - November 7, 2014 Category: Genetics & Stem Cells Source Type: research
Consanguinity and Primary Immunodeficiencies
Primary immunodeficiencies (PIDs) are a heterogeneous group of genetic disorders caused by defects in the immune system that predispose patients to infections, autoimmune diseases, lymphoproliferation and malignancies. Most PIDs are inherited in an autosomal recessive pattern; therefore, they are more common in areas with high rates of consanguineous marriage. Reports about PIDs from these areas have demonstrated a peculiar prevalence of more severe forms of diseases compared to other regions, and patients born to consanguineous parents have increased rates of morbidity and mortality compared to other patients. Individuals...
Source: Human Heredity - November 7, 2014 Category: Genetics & Stem Cells Source Type: research
The kinship2 R Package for Pedigree Data
Conclusion: We make the kinship2 package available for R on the Contributed R Archives Network (CRAN), where data management is built-in and other packages can use the pedigree object.Hum Hered 2014;78:91-93 (Source: Human Heredity)
Source: Human Heredity - November 7, 2014 Category: Genetics & Stem Cells Source Type: research
Using Gene Expression to Improve the Power of Genome-Wide Association Analysis
Background/Aims: Genome-wide association (GWA) studies have reported susceptible regions in the human genome for many common diseases and traits; however, these loci only explain a minority of trait heritability. To boost the power of a GWA study, substantial research endeavors have been focused on integrating other available genomic information in the analysis. Advances in high through-put technologies have generated a wealth of genomic data and made combining SNP and gene expression data become feasible. Results: In this paper, we propose a novel procedure to incorporate gene expression information into GWA analysis. Thi...
Source: Human Heredity - November 7, 2014 Category: Genetics & Stem Cells Source Type: research
