Dataset Information

Estimation of intrafamilial DNA contamination in family trio genome sequencing using deviation from Mendelian inheritance.

ABSTRACT: With the increasing number of sequencing projects involving families, quality control tools optimized for family genome sequencing are needed. However, accurately quantifying contamination in a DNA mixture is particularly difficult when genetically related family members are the sources. We developed TrioMix, a maximum likelihood estimation (MLE) framework based on Mendel's law of inheritance, to quantify DNA mixture between family members in genome sequencing data of parent-offspring trios. TrioMix can accurately deconvolute any intrafamilial DNA contamination, including parent-offspring, sibling-sibling, parent-parent, and even multiple familial sources. In addition, TrioMix can be applied to detect genomic abnormalities that deviate from Mendelian inheritance patterns, such as uniparental disomy (UPD) and chimerism. A genome-wide depth and variant allele frequency plot generated by TrioMix facilitates tracing the origin of Mendelian inheritance deviations. We showed that TrioMix could accurately deconvolute genomes in both simulated and real data sets.

SUBMITTER: Yoon CJ

PROVIDER: S-EPMC9808622 | biostudies-literature | 2022 Nov-Dec

REPOSITORIES: biostudies-literature

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Estimation of intrafamilial DNA contamination in family trio genome sequencing using deviation from Mendelian inheritance.

Yoon Christopher J CJ Kim Su Yeon SY Nam Chang Hyun CH Lee Junehawk J Park Jung Woo JW Mun Jihyeob J Park Seongyeol S Lee Soyoung S Yi Boram B Min Kyoung Il KI Wiley Brian B Bolton Kelly L KL Lee Jeong Ho JH Kim Eunjoon E Yoo Hee Jeong HJ Jun Jong Kwan JK Choi Ji Seon JS Griffith Malachi M Griffith Obi L OL Ju Young Seok YS

Genome research 20221101 11-12

With the increasing number of sequencing projects involving families, quality control tools optimized for family genome sequencing are needed. However, accurately quantifying contamination in a DNA mixture is particularly difficult when genetically related family members are the sources. We developed TrioMix, a maximum likelihood estimation (MLE) framework based on Mendel's law of inheritance, to quantify DNA mixture between family members in genome sequencing data of parent-offspring trios. Tri ...[more]

PMID: 36617634

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Project description:Parkinson's disease is a common, progressive neurodegenerative disorder, affecting 3% of those older than 75 years of age. Clinically, Parkinson's disease (PD) is associated with resting tremor, postural instability, rigidity, bradykinesia, and a good response to levodopa therapy. Over the last 15 years, numerous studies have confirmed that genetic factors contribute to the complex pathogenesis of PD. Highly penetrant mutations producing rare, monogenic forms of the disease have been discovered in singular genes such as SNCA, Parkin, DJ-1, PINK 1, LRRK2, and VPS35. Unique variants with incomplete penetrance in LRRK2 and GBA have been shown to be strong risk factors for PD in certain populations. Additionally, over 20 common variants with small effect sizes are now recognized to modulate the risk for PD. Investigating Mendelian forms of PD has provided precious insight into the pathophysiology that underlies the more common idiopathic form of disease; however, no treatment methodologies have developed. Furthermore, for identified common risk alleles, the functional basis underlying risk principally remains unknown. The challenge over the next decade will be to strengthen the findings delivered through genetic discovery by assessing the direct, biological consequences of risk variants in tandem with additional high-content, integrated datasets. This review discusses monogenic risk factors and mechanisms of Mendelian inheritance of Parkinson disease. Highly penetrant mutations in SNCA, Parkin, DJ-1, PINK 1, LRRK2 and VPS35 produce rare, monogenic forms of the disease, while unique variants within LRRK2 and GBA show incomplete penetrance and are strong risk factors for PD. Additionally, over 20 common variants with small effect sizes modulate disease risk. The challenge over the next decade is to strengthen genetic findings by assessing direct, biological consequences of risk variants in tandem with high-content, integrated datasets. This article is part of a special issue on Parkinson disease.

Dataset Information

Estimation of intrafamilial DNA contamination in family trio genome sequencing using deviation from Mendelian inheritance.

Publications

Estimation of intrafamilial DNA contamination in family trio genome sequencing using deviation from Mendelian inheritance.

Similar Datasets

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