Copy number variations in the genome of the Qatari population

Fakhro, Khalid; Yousri, Noha A.; Rodríguez-Flores, Juan L.; Robay, Amal; Staudt, Michelle R.; Agosto-Perez, Francisco; Salit, Jacqueline; Malek, Joel A.; Suhre, Karsten; Jayyousi, Amin; Zirie, Mahmoud; Stadler, Dora J.; Mezey, Jason G.; Crystal, Ronald G.

doi:10.1186/s12864-015-1991-5

Cited by 9 publications

(12 citation statements)

References 56 publications

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“…The efficacy of this array was rather poor, with 40.54% of CNVs that were tagged at r 2 > 0.5 and 21.17% in strong LD. Similar findings were observed in the CNV study in the Qatari population when using the Illumina OMNI2.5M array 16 . This taggability gap could be attributed to the local SNP density paucity, thus influencing the LD level.…”

Section: Discussionsupporting

confidence: 86%

“…A comparative LD analysis using two different SNP sets genotyped by different SNP arrays revealed that ~80% of CNVs are in high LD ( r 2 > 0.8) when HapMap phase 2 SNP set was used compared to ~50% of CNVs that were in high LD with commercial SNP array sets 18 . An improvement of this taggability has been obtained with whole-genome sequencing SNPs as >70% of the deletions have been tagged by at least one SNP at r 2 > 0.5 and over 50% at r 2 > 0.8 in the Qatari dataset in agreement with LD data generated using 1000 Genome dataset 15 , 16 . Consequently, this fact suggests that CNV genotyping could be challenging using this or other commercial arrays in North African populations.…”

Section: Discussionsupporting

confidence: 63%

“…Studies focusing on the characterization of CNVs in the Arab World are not available, except one on the Qatari population 16 . In this study, we applied Affymetrix Genome-Wide Human SNP Array 6.0, which was designed for both SNP and CNV detection, to explore genome-wide CNV in the Tunisian population.…”

Section: Introductionmentioning

confidence: 99%

“…In order to understand the extent to which CNVs influence phenotypes, deep analyses in both patient and healthy individuals are required. Different approaches, including quantification of hybridization to specific oligonucleotides 13 , clone arrays 14 , direct genome sequencing 15,16 , and single-nucleotide polymorphism (SNP) array [17][18][19] , allowed to explore CNVs, thus providing their global estimates of frequencies, distribution, and functional features in large population cohorts and HapMap samples 1,2,4,16,[19][20][21][22][23][24][25][26][27][28][29] . Although medical and clinical genetic studies have been widely performed in the Arab World known to display high rates of consanguinity and endogamy, little attention has been paid to potential variations linked to health in the region 30,31 .…”

Section: Introductionmentioning

confidence: 99%

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A map of copy number variations in the Tunisian population: a valuable tool for medical genomics in North Africa

et al. 2021

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Copy number variation (CNV) is considered as the most frequent type of structural variation in the human genome. Some CNVs can act on human phenotype diversity, encompassing rare Mendelian diseases and genomic disorders. The North African populations remain underrepresented in public genetic databases in terms of single-nucleotide variants as well as for larger genomic mutations. In this study, we present the first CNV map for a North African population using the Affymetrix Genome-Wide SNP (single-nucleotide polymorphism) array 6.0 array genotyping intensity data to call CNVs in 102 Tunisian healthy individuals. Two softwares, PennCNV and Birdsuite, were used to call CNVs in order to provide reliable data. Subsequent bioinformatic analyses were performed to explore their features and patterns. The CNV map of the Tunisian population includes 1083 CNVs spanning 61.443 Mb of the genome. The CNV length ranged from 1.017 kb to 2.074 Mb with an average of 56.734 kb. Deletions represent 57.43% of the identified CNVs, while duplications and the mixed loci are less represented. One hundred and three genes disrupted by CNVs are reported to cause 155 Mendelian diseases/phenotypes. Drug response genes were also reported to be affected by CNVs. Data on genes overlapped by deletions and duplications segments and the sequence properties in and around them also provided insights into the functional and health impacts of CNVs. These findings represent valuable clues to genetic diversity and personalized medicine in the Tunisian population as well as in the ethnically similar populations from North Africa.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A map of copy number variations in the Tunisian population: a valuable tool for medical genomics in North Africa

et al. 2021

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“…The superior performance of cn.MOPS on WGS and WES data has already been demonstrated (Guo et al., ; Klambauer et al., ). Specifically, cn.MOPS has been used to detect CNVs in the Taiwanese Han and Qatari populations (Fakhro et al., ; Lin, Tseng, Jeng, & Sun, ), in individuals with intellectual disability (Schuurs‐Hoeijmakers et al., ), and in patients with early‐onset neuropsychiatric disorders (Brand et al., ). cn.MOPS builds a local model that captures the read characteristics of each ROI.…”

Section: Introductionmentioning

confidence: 99%

panelcn.MOPS: Copy-number detection in targeted NGS panel data for clinical diagnostics

et al. 2017

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Targeted next‐generation‐sequencing (NGS) panels have largely replaced Sanger sequencing in clinical diagnostics. They allow for the detection of copy‐number variations (CNVs) in addition to single‐nucleotide variants and small insertions/deletions. However, existing computational CNV detection methods have shortcomings regarding accuracy, quality control (QC), incidental findings, and user‐friendliness. We developed panelcn.MOPS, a novel pipeline for detecting CNVs in targeted NGS panel data. Using data from 180 samples, we compared panelcn.MOPS with five state‐of‐the‐art methods. With panelcn.MOPS leading the field, most methods achieved comparably high accuracy. panelcn.MOPS reliably detected CNVs ranging in size from part of a region of interest (ROI), to whole genes, which may comprise all ROIs investigated in a given sample. The latter is enabled by analyzing reads from all ROIs of the panel, but presenting results exclusively for user‐selected genes, thus avoiding incidental findings. Additionally, panelcn.MOPS offers QC criteria not only for samples, but also for individual ROIs within a sample, which increases the confidence in called CNVs. panelcn.MOPS is freely available both as R package and standalone software with graphical user interface that is easy to use for clinical geneticists without any programming experience. panelcn.MOPS combines high sensitivity and specificity with user‐friendliness rendering it highly suitable for routine clinical diagnostics.

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Mutation spectrum of congenital heart disease in a consanguineous Turkish population

Dong

Kaymakçalan

Jin

et al. 2022

Molec Gen & Gen Med

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Backgrounds While many studies agree that consanguinity increases the rate of congenital heart disease (CHD), few genome analyses have been conducted with consanguineous CHD cohorts. Methods We recruited 73 CHD probands from consanguineous families in Turkey and used whole‐exome sequencing (WES) to identify genetic lesions in these patients. Results On average, each patient had 6.95 rare damaging homozygous variants, 0.68 of which are loss‐of‐function (LoF) variants. Seven patients (9.6%) carried damaging homozygous variants in five causal CHD genes. Six of those patients exhibited laterality defects (six HTX and one D‐TGA). Three additional patients (4.1%) harbored other types of CHD‐associated genomic alterations, which overall explained 13.7% (10/73) of the cohort. The contribution from recessive variants in our cohort is higher than 1.8% reported from a cohort of 2871 CHD subjects where 5.6% of subjects met the criteria for consanguinity. Conclusions Our WES screen of a Turkish consanguineous population with structural CHD revealed its unique genetic architecture. Six of seven damaging homozygous variants in CHD causal genes occur in the setting of laterality defects implies a strong contribution from consanguinity to these defects specifically. Our study thus provided valuable information about the genetic landscape of CHD in consanguineous families in Turkey.

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Copy number variations in the genome of the Qatari population

Cited by 9 publications

References 56 publications

A map of copy number variations in the Tunisian population: a valuable tool for medical genomics in North Africa

A map of copy number variations in the Tunisian population: a valuable tool for medical genomics in North Africa

panelcn.MOPS: Copy-number detection in targeted NGS panel data for clinical diagnostics

Mutation spectrum of congenital heart disease in a consanguineous Turkish population

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