Genetic testing and reports on nucleotide alterations in the Iranian population are still limited. No mutations were found in the APOB gene, whereas several silent mutations/polymorphisms were identified in the LDLR and PCSK9 genes. This study is the first to identify 1 pathogenic mutation in the LDLR gene (c.1014C > G ) and to cosegregate it from the affected individual in the family. Six different point mutations (p.Cys148Tyr, p.Cys216Tyr, p.Cys302Trp, p.Cys338Trp, p.Leu479Gln, and p.G593Afs ∗72) in LDLR and a double mutation (p.Asp172His and p.Ala53Val) in both LDLR and PCSK9 genes were identified in seven families with clinically diagnosed FH (43%), whereas no pathogenic mutations were found in eight families with clinically diagnosed FH. The pathogenicity of the identified mutations was investigated via either segregation analyses in the family or in silico predictive software. Direct DNA sequencing was applied to screen the whole coding exons and exon–intron boundaries of the LDLR and PCSK9 genes and the main parts of their introns, together with exon 26 of the APOB gene. Fifteen unrelated individuals with a clinical diagnosis of FH and premature CAD were recruited. In the present study, we screened the nucleotide variations of the LDLR and PCSK9 genes, as well as a part of the APOB gene, in Iranian patients with FH and premature CAD to find the genetic cause of the disorder. 3Laboratory of Biochemical Neuroendocrinology, Montreal Clinical Research Institute, University of Montreal, Montreal, QC, Canadaįamilial hypercholesterolemia (FH) is a common, yet underdiagnosed, genetic disorder characterized by lifelong elevated low-density lipoprotein cholesterol levels, which can increase the risk of early-onset coronary artery disease (CAD).2Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.1Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.However, for TOPMed sequence data, Beagle is more than 20 times faster than SHAPEIT, achieves similar accuracy, and scales to larger sample sizes.Arman Moradi 1, Majid Maleki 2, Zahra Ghaemmaghami 2, Zahra Khajali 2, Feridoun Noohi 2, Maryam Hosseini Moghadam 2, Samira Kalyinia 2, Seyed Javad Mowla 1, Nabil G. Both methods have very similar accuracy and computation time for UK Biobank SNP array data. We compare Beagle 5.2 and SHAPEIT 4.2.1 by using expanding subsets of 485,301 UK Biobank samples and 38,387 TOPMed samples.
BIOEDIT CODE HETEROZYGOTE SOFTWARE
This haplotype phasing method is implemented in the open-source Beagle 5.2 software package.
For data with many low-frequency variants, such as whole-genome sequence data, the method employs a two-stage phasing algorithm that phases high-frequency markers via progressive phasing in the first stage and phases low-frequency markers via genotype imputation in the second stage.
It incorporates a progressive phasing algorithm that identifies confidently phased heterozygotes in each iteration and fixes the phase of these heterozygotes in subsequent iterations.
The method uses marker windowing and composite reference haplotypes to reduce memory usage and computation time. We present a fast, accurate, and memory-efficient haplotype phasing method that scales to large-scale SNP array and sequence data. Haplotype phasing is the estimation of haplotypes from genotype data.