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Review
. 2021 May 28;12(6):827.
doi: 10.3390/genes12060827.

Focused Strategies for Defining the Genetic Architecture of Congenital Heart Defects

Lisa J Martin  1   2 , D Woodrow Benson  3
Affiliations
Review

Focused Strategies for Defining the Genetic Architecture of Congenital Heart Defects

Lisa J Martin et al. Genes (Basel). .

Abstract

Congenital heart defects (CHD) are malformations present at birth that occur during heart development. Increasing evidence supports a genetic origin of CHD, but in the process important challenges have been identified. This review begins with information about CHD and the importance of detailed phenotyping of study subjects. To facilitate appropriate genetic study design, we review DNA structure, genetic variation in the human genome and tools to identify the genetic variation of interest. Analytic approaches powered for both common and rare variants are assessed. While the ideal outcome of genetic studies is to identify variants that have a causal role, a more realistic goal for genetic analytics is to identify variants in specific genes that influence the occurrence of a phenotype and which provide keys to open biologic doors that inform how the genetic variants modulate heart development. It has never been truer that good genetic studies start with good planning. Continued progress in unraveling the genetic underpinnings of CHD will require multidisciplinary collaboration between geneticists, quantitative scientists, clinicians, and developmental biologists.

Keywords: association; cardiovascular malformations; etiology; genetic variation; phenotyping.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Illustration of DNA organization, types of variation present, and capture of variants using differing technologies.
See this image and copyright information in PMC

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