Modifier genes in Mendelian disorders

The example of cystic fibrosis

Research output: Contribution to journalArticle

Abstract

In the past three decades, scientists have had immense success in identifying genes and their variants that contribute to an array of diseases. While the identification of such genetic variants has informed our knowledge of the etiologic bases of diseases, there continues to be a substantial gap in our understanding of the factors that modify disease severity. Monogenic diseases provide an opportunity to identify modifiers as they have uniform etiology, detailed phenotyping of affected individuals, and familial clustering. Cystic fibrosis (CF) is among the more common life-shortening recessive disorders that displays wide variability in clinical features and survival. Considerable progress has been made in elucidating the contribution of genetic and nongenetic factors to CF. Allelic variation in CFTR, the gene responsible for CF, correlates with some aspects of the disease. However, lung function, neonatal intestinal obstruction, diabetes, and anthropometry display strong genetic control independent of CFTR, and candidate gene studies have revealed genetic modifiers underlying these traits. The application of genome-wide techniques holds great promise for the identification of novel genetic variants responsible for the heritable features and complications of CF. Since the genetic modifiers are known to alter the course of disease, their protein products become immediate targets for therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)57-69
Number of pages13
JournalAnnals of the New York Academy of Sciences
Volume1214
Issue number1
DOIs
StatePublished - Dec 2010

Fingerprint

Modifier Genes
Cystic Fibrosis
Genes
Anthropometry
Knowledge Bases
Intestinal Obstruction
Medical problems
Cluster Analysis
Gene
Modifier
Genome
Lung

Keywords

  • Candidate gene
  • Genome wide
  • Heritability
  • Variation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Modifier genes in Mendelian disorders : The example of cystic fibrosis. / Cutting, Garry R.

In: Annals of the New York Academy of Sciences, Vol. 1214, No. 1, 12.2010, p. 57-69.

Research output: Contribution to journalArticle

@article{8b81476ca6f642b1bed81bf4a5124fd7,
title = "Modifier genes in Mendelian disorders: The example of cystic fibrosis",
abstract = "In the past three decades, scientists have had immense success in identifying genes and their variants that contribute to an array of diseases. While the identification of such genetic variants has informed our knowledge of the etiologic bases of diseases, there continues to be a substantial gap in our understanding of the factors that modify disease severity. Monogenic diseases provide an opportunity to identify modifiers as they have uniform etiology, detailed phenotyping of affected individuals, and familial clustering. Cystic fibrosis (CF) is among the more common life-shortening recessive disorders that displays wide variability in clinical features and survival. Considerable progress has been made in elucidating the contribution of genetic and nongenetic factors to CF. Allelic variation in CFTR, the gene responsible for CF, correlates with some aspects of the disease. However, lung function, neonatal intestinal obstruction, diabetes, and anthropometry display strong genetic control independent of CFTR, and candidate gene studies have revealed genetic modifiers underlying these traits. The application of genome-wide techniques holds great promise for the identification of novel genetic variants responsible for the heritable features and complications of CF. Since the genetic modifiers are known to alter the course of disease, their protein products become immediate targets for therapeutic intervention.",
keywords = "Candidate gene, Genome wide, Heritability, Variation",
author = "Cutting, {Garry R}",
year = "2010",
month = "12",
doi = "10.1111/j.1749-6632.2010.05879.x",
language = "English (US)",
volume = "1214",
pages = "57--69",
journal = "Annals of the New York Academy of Sciences",
issn = "0077-8923",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Modifier genes in Mendelian disorders

T2 - The example of cystic fibrosis

AU - Cutting, Garry R

PY - 2010/12

Y1 - 2010/12

N2 - In the past three decades, scientists have had immense success in identifying genes and their variants that contribute to an array of diseases. While the identification of such genetic variants has informed our knowledge of the etiologic bases of diseases, there continues to be a substantial gap in our understanding of the factors that modify disease severity. Monogenic diseases provide an opportunity to identify modifiers as they have uniform etiology, detailed phenotyping of affected individuals, and familial clustering. Cystic fibrosis (CF) is among the more common life-shortening recessive disorders that displays wide variability in clinical features and survival. Considerable progress has been made in elucidating the contribution of genetic and nongenetic factors to CF. Allelic variation in CFTR, the gene responsible for CF, correlates with some aspects of the disease. However, lung function, neonatal intestinal obstruction, diabetes, and anthropometry display strong genetic control independent of CFTR, and candidate gene studies have revealed genetic modifiers underlying these traits. The application of genome-wide techniques holds great promise for the identification of novel genetic variants responsible for the heritable features and complications of CF. Since the genetic modifiers are known to alter the course of disease, their protein products become immediate targets for therapeutic intervention.

AB - In the past three decades, scientists have had immense success in identifying genes and their variants that contribute to an array of diseases. While the identification of such genetic variants has informed our knowledge of the etiologic bases of diseases, there continues to be a substantial gap in our understanding of the factors that modify disease severity. Monogenic diseases provide an opportunity to identify modifiers as they have uniform etiology, detailed phenotyping of affected individuals, and familial clustering. Cystic fibrosis (CF) is among the more common life-shortening recessive disorders that displays wide variability in clinical features and survival. Considerable progress has been made in elucidating the contribution of genetic and nongenetic factors to CF. Allelic variation in CFTR, the gene responsible for CF, correlates with some aspects of the disease. However, lung function, neonatal intestinal obstruction, diabetes, and anthropometry display strong genetic control independent of CFTR, and candidate gene studies have revealed genetic modifiers underlying these traits. The application of genome-wide techniques holds great promise for the identification of novel genetic variants responsible for the heritable features and complications of CF. Since the genetic modifiers are known to alter the course of disease, their protein products become immediate targets for therapeutic intervention.

KW - Candidate gene

KW - Genome wide

KW - Heritability

KW - Variation

UR - http://www.scopus.com/inward/record.url?scp=78650404224&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650404224&partnerID=8YFLogxK

U2 - 10.1111/j.1749-6632.2010.05879.x

DO - 10.1111/j.1749-6632.2010.05879.x

M3 - Article

VL - 1214

SP - 57

EP - 69

JO - Annals of the New York Academy of Sciences

JF - Annals of the New York Academy of Sciences

SN - 0077-8923

IS - 1

ER -