Complex Genetic Architecture Revealed by Analysis of High-Density Lipoprotein Cholesterol in Chromosome Substitution Strains and F^sub 2^ Crosses

By Stylianou, Ioannis M.; Tsaih, Shirng-Wern et al. | Genetics, October 2006 | Go to article overview

Complex Genetic Architecture Revealed by Analysis of High-Density Lipoprotein Cholesterol in Chromosome Substitution Strains and F^sub 2^ Crosses


Stylianou, Ioannis M., Tsaih, Shirng-Wern, DiPetrillo, Keith, Ishimori, Naoki, et al., Genetics


ABSTRACT

Intercrosses between inbred lines provide a traditional approach to analysis of polygenic inheritance in model organisms. Chromosome substitution strains (CSSs) have been developed as an alternative to accelerate the pace of gene identification in quantitative trait mapping. We compared a classical intercross and three CSS intercrosses to examine the genetic architecture underlying plasma high-density lipoprotein cholesterol (HDL) levels in the C57BL/6J (B) and A/J (A) mouse strains. The B × A intercross revealed significant quantitative trait loci (QTL) for HDL on chromosomes 1, 4, 8, 15, 17, 18, and 19. A CSS survey revealed that many have significantly different HDL levels compared to the background strain B, including chromosomes with no significant QTL in the intercross and, in some cases (CSS-1, CSS-17), effects that are opposite to those observed in the B × A intercross population. Intercrosses between B and three CSSs (CSS-3, CSS-11, and CSS-8) revealed significant QTL but with some unexpected differences from the B × A intercross. Our inability to predict the results of CSS intercrosses suggests that additional complexity will be revealed by further crosses and that the CSS mapping strategy should be viewed as a complement to, rather than a replacement for, classical intercross mapping.

THE genomewide distribution of allelic variation in an intercross population, as in human populations, provides great potential for epistatic interactions that can mask or enhance the impact of allelic variation at multiple loci. This complexity may hinder our ability to detect the genes and alleles that are most important. One approach to circumvent this possibility is to reduce the number of potential interactions by reducing the amount of segregating variation in a cross. Chromosome substitution strain (CSS, also known as consomic) panels achieve this goal by restricting variation to a single chromosome (Nadeau et al. 2000; Cowley et al. 2004; Fernandes et al. 2004; Bevova et al. 2006). In these panels each strain is derived from a "background" inbred strain except a single chromosome that is derived from a distinct "donor" inbred strain. Consequently any genetic variation seen among CSSs is presumably due to allelic variation on the donor chromosome. It is possible that some differences between the CSSs may be due to recent mutations (Cook et al. 2006). However, it is estimated that only 3% of polymorphisms among strains have arisen within the past 100 years. Thus, most of the differences between inbred strains, and specifically for this report between C57BL/6J (B) and A/J (A), are ancestral and differences among consomic strains due to recent mutations are expected to be quite rare (Frazer et al. 2004).

Ischemic cardiovascular disease (ICD) is the leading cause of morbidity and mortality in developed nations. Major risk factors for ICD are high levels of low-density lipoprotein cholesterol (LDL) and low levels of high-density lipoprotein cholesterol (HDL) in plasma (Fruchart and Duriez 2002). High levels of plasma HDL provide protection against heart disease as shown in both human (Gordon et al. 1989; Wilson et al. 1994; Nissen et al. 2003) and animal studies (Badimon et al. 1990; Rubin et al. 1991; Plump et al. 1994; Sugano et al. 1998; Okamoto et al. 2000; Rittershaus et al. 2000). A successful route toward identifying genes that affect quantitative phenotypes such as HDL levels is through the use of inbred mouse strains and quantitative trait locus (QTL) analysis. A combination of genetic tools and techniques is helping to identify these QTL genes (Korstanje and Paigen 2002; Dipetrillo et al. 2005; Hillebrandt et al. 2005;Wang et al. 2005). A total of 22 mapping crosses have identified .130 loci for HDL and these localize to 37 unique QTL (Wang and Paigen 2005). Only a small number of gene-by-gene interactions have been reported for HDL (Ishimori et al. 2004), in comparison to other traits such as obesity (Cheverud et al. …

The rest of this article is only available to active members of Questia

Sign up now for a free, 1-day trial and receive full access to:

  • Questia's entire collection
  • Automatic bibliography creation
  • More helpful research tools like notes, citations, and highlights
  • Ad-free environment

Already a member? Log in now.

Notes for this article

Add a new note
If you are trying to select text to create highlights or citations, remember that you must now click or tap on the first word, and then click or tap on the last word.
One moment ...
Default project is now your active project.
Project items

Items saved from this article

This article has been saved
Highlights (0)
Some of your highlights are legacy items.

Highlights saved before July 30, 2012 will not be displayed on their respective source pages.

You can easily re-create the highlights by opening the book page or article, selecting the text, and clicking “Highlight.”

Citations (0)
Some of your citations are legacy items.

Any citation created before July 30, 2012 will labeled as a “Cited page.” New citations will be saved as cited passages, pages or articles.

We also added the ability to view new citations from your projects or the book or article where you created them.

Notes (0)
Bookmarks (0)

You have no saved items from this article

Project items include:
  • Saved book/article
  • Highlights
  • Quotes/citations
  • Notes
  • Bookmarks
Notes
Cite this article

Cited article

Style
Citations are available only to our active members.
Sign up now to cite pages or passages in MLA, APA and Chicago citation styles.

(Einhorn, 1992, p. 25)

(Einhorn 25)

1

1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25, http://www.questia.com/read/27419298.

Cited article

Complex Genetic Architecture Revealed by Analysis of High-Density Lipoprotein Cholesterol in Chromosome Substitution Strains and F^sub 2^ Crosses
Settings

Settings

Typeface
Text size Smaller Larger Reset View mode
Search within

Search within this article

Look up

Look up a word

  • Dictionary
  • Thesaurus
Please submit a word or phrase above.
Print this page

Print this page

Why can't I print more than one page at a time?

Full screen

matching results for page

Cited passage

Style
Citations are available only to our active members.
Sign up now to cite pages or passages in MLA, APA and Chicago citation styles.

"Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn, 1992, p. 25).

"Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn 25)

"Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences."1

1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25, http://www.questia.com/read/27419298.

Cited passage

Welcome to the new Questia Reader

The Questia Reader has been updated to provide you with an even better online reading experience.  It is now 100% Responsive, which means you can read our books and articles on any sized device you wish.  All of your favorite tools like notes, highlights, and citations are still here, but the way you select text has been updated to be easier to use, especially on touchscreen devices.  Here's how:

1. Click or tap the first word you want to select.
2. Click or tap the last word you want to select.

OK, got it!

Thanks for trying Questia!

Please continue trying out our research tools, but please note, full functionality is available only to our active members.

Your work will be lost once you leave this Web page.

For full access in an ad-free environment, sign up now for a FREE, 1-day trial.

Already a member? Log in now.