Focused Strategies for Defining the Genetic Architecture of Congenital Heart Defects.

D. Woodrow Benson,Lisa J. Martin

doi:10.3390/genes12060827

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.

Highlights

The objective of this review is to provide an overview of strategies utilized in pursuit of defining the genetic origins of rare birth defects characterized by malformation of the heart, so-called congenital heart defects (CHD)
We hope that review of focused strategies will facilitate studies that improve our understanding of the genetic architecture of human CHD
As recently reviewed [3], while considerable progress has been made in defining the genetic underpinnings of CHD, significant work remains

Summary

Introduction

The objective of this review is to provide an overview of strategies utilized in pursuit of defining the genetic origins of rare birth defects characterized by malformation of the heart, so-called congenital heart defects (CHD). CHD occurs during heart development, known as cardiogenesis, which begins very early in gestation. Identification of the regulatory networks controlling all stages of cardiogenesis has led to improved understanding of genes involved in heart development [2]. Complimentary, genetic studies of CHD patients have identified variants in genes essential to heart development [3].

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