NDLI: Genotype–Phenotype Map Characteristics of an In silico Heart Cell

Content Provider	PubMed Central
Author	Vik, Jon Olav Gjuvsland, Arne B. Li, Liren Kristin, Tøndel Niederer, Steven Smith, Nicolas P. Hunter, Peter J. Omholt, Stig W.
Copyright Year	2011
Abstract	Understanding the causal chain from genotypic to phenotypic variation is a tremendous challenge with huge implications for personalized medicine. Here we argue that linking computational physiology to genetic concepts, methodology, and data provides a new framework for this endeavor. We exemplify this causally cohesive genotype–phenotype (cGP) modeling approach using a detailed mathematical model of a heart cell. In silico genetic variation is mapped to parametric variation, which propagates through the physiological model to generate multivariate phenotypes for the action potential and calcium transient under regular pacing, and ion currents under voltage clamping. The resulting genotype-to-phenotype map is characterized using standard quantitative genetic methods and novel applications of high-dimensional data analysis. These analyses reveal many well-known genetic phenomena like intralocus dominance, interlocus epistasis, and varying degrees of phenotypic correlation. In particular, we observe penetrance features such as the masking/release of genetic variation, so that without any change in the regulatory anatomy of the model, traits may appear monogenic, oligogenic, or polygenic depending on which genotypic variation is actually present in the data. The results suggest that a cGP modeling approach may pave the way for a computational physiological genomics capable of generating biological insight about the genotype–phenotype relation in ways that statistical-genetic approaches cannot.
Related Links	http://dx.doi.org/10.3389/fphys.2011.00106
Starting Page	106
File Format	PDF
ISSN	1664042X
e-ISSN	1664042X
Journal	Frontiers in Physiology
Volume Number	2
Language	English
Publisher	Frontiers Research Foundation
Publisher Date	2011-01-01
Access Restriction	Open
Rights Holder	Frontiers Research Foundation
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Physiology Physiology (medical)

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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