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Systems Genetic Analysis of Multi-parent Crosses

Award Number: R01GM070683
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2004
PERIOD OF PERFORMANCE END DATE: 07/31/2024

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Systems Genetic Analysis of Multi-parent Crosses - PROJECT SUMMARY/ABSTRACT Forward genetic studies using animal models represent an important tool for the discovery of physiological and biochemical mechanisms that cause human disease. Genetic studies in model organisms complement direct human studies, with advantages that include the ability to apply experimental perturbations and to control both environmental conditions and genetic makeup of study populations. Access to disease-relevant tissues provides opportunities for large-scale molecular profiling and deep physiological phenotyping. Traditional forward genetic experiments in animal models employed crosses between two inbred strains. New genetic populations, derived from more than two founder strains, are being developed for rodents and other model organisms to serve as community resources for systems genetics studies. These multi-parent populations provide improved mapping precision, and their greater genetic variability enables their use for a broader set of disease phenotypes than any one bi-parental population. Multi-parent populations present new analytical challenges, including haplotype reconstruction, the treatment of multiple founder alleles, the need to account for population structure, the use of the distribution of SNP alleles across founder strains to home in on causal SNPs. High dimensional phenotypes present additional challenges and opportunities, with each new technology requiring special care, but with mediation analysis and causal network modeling providing valuable insights into possible disease mechanisms. Software tools that implement the best analysis methods and make them readily accessible, along with interactive data analysis and visualization tools that enable exploration of these high-dimensional data, empower researchers to explore systems genetics data on multi-parent populations. With these general goals, our specific aims are to (1) Develop statistical methods for the genetic analysis of multi-parent cross designs, including methods for haplotype reconstruction with low-pass genotyping-by- sequencing data, identification of subsets of causal SNPs underlying a QTL, multiple-QTL modeling, and the dissection of contributions to heritability; (2) Develop statistical methods for genetic analysis of high- dimensional phenotypes, including mediation analysis and causal network modeling; and (3) Develop next- generation software for system genetic analysis with high-dimensional data, including multi-parent populations and interactive data visualization tools. These aims will support and facilitate the growing use of genetically diverse multi-parent populations in biomedical research.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2022	JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Biomedical Research and Research Training	000	16	3/6/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $492,343 )
2022	2022	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Biomedical Research and Research Training	000	16	7/20/2022	NON-COMPETING CONTINUATION	$492,343
														Subtotal = $492,343

Issue Date FY: 2021 ( Subtotal = $492,343 )
2021	2021	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Biomedical Research and Research Training	000	15	7/20/2021	NON-COMPETING CONTINUATION	$492,343
														Subtotal = $492,343

Issue Date FY: 2020 ( Subtotal = $491,886 )
2020	2020	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Biomedical Research and Research Training	000	14	8/20/2020	NON-COMPETING CONTINUATION	$491,886
														Subtotal = $491,886

Issue Date FY: 2019 ( Subtotal = $526,749 )
2019	2019	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Biomedical Research and Research Training	001	13	9/13/2019	COMPETING CONTINUATION	$526,795
2019	2018	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Biomedical Research and Research Training	000	12	7/22/2019	SUPPLEMENT FOR EXPANSION	-$46
														Subtotal = $526,749

Issue Date FY: 2018 ( Subtotal = $557,037 )
2018	2018	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Biomedical Research and Research Training	001	12	6/4/2018	NON-COMPETING CONTINUATION	$49,641
2018	2018	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Biomedical Research and Research Training	000	12	3/23/2018	NON-COMPETING CONTINUATION	$446,772
2018	2018	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Biomedical Research and Research Training	002	12	9/19/2018	SUPPLEMENT FOR EXPANSION	$60,624
														Subtotal = $557,037

Issue Date FY: 2017 ( Subtotal = $496,376 )
2017	2017	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Biomedical Research and Research Training	001	11	6/20/2017	NON-COMPETING CONTINUATION	$49,638
2017	2017	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Biomedical Research and Research Training	000	11	3/28/2017	NON-COMPETING CONTINUATION	$446,738
														Subtotal = $496,376

Issue Date FY: 2016 ( Subtotal = $495,054 )
2016	2016	JACKSON LABORATORY (THE)	600 MAIN STREET	BAR HARBOR	ME	04609	HANCOCK	USA	Biomedical Research and Research Training	000	10	3/21/2016	NON-COMPETING CONTINUATION	$495,054
														Subtotal = $495,054

Issue Date FY: 2015 ( Subtotal = $536,936 )
2015	2015	JACKSON LABORATORY (THE)	600 MAIN STREET	BAR HARBOR	ME	04609	HANCOCK	USA	Biomedical Research and Research Training	001	9	3/24/2015	COMPETING CONTINUATION	$536,936
2015	2012	JACKSON LABORATORY (THE)	600 MAIN STREET	BAR HARBOR	ME	04609	HANCOCK	USA	Biomedical Research and Research Training	000	8	3/19/2015	NON-COMPETING CONTINUATION	$0
														Subtotal = $536,936

Issue Date FY: 2014 ( Subtotal = $0 )
2014	2012	JACKSON LABORATORY (THE)	600 MAIN STREET	BAR HARBOR	ME	04609	HANCOCK	USA	Biomedical Research and Research Training	000	8	7/10/2014	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2012 ( Subtotal = $341,075 )
2012	2012	JACKSON LABORATORY (THE)	600 MAIN STREET	BAR HARBOR	ME	04609	HANCOCK	USA	Biomedical Research and Research Training	000	8	6/18/2012	NON-COMPETING CONTINUATION	$341,075
														Subtotal = $341,075

Issue Date FY: 2011 ( Subtotal = $341,075 )
2011	2011	JACKSON LABORATORY (THE)	600 MAIN STREET	BAR HARBOR	ME	04609	HANCOCK	USA	Biomedical Research and Research Training	000	7	6/20/2011	NON-COMPETING CONTINUATION	$341,075
														Subtotal = $341,075

Issue Date FY: 2010 ( Subtotal = $344,520 )
2010	2010	JACKSON LABORATORY (THE)	600 MAIN STREET	BAR HARBOR	ME	04609	HANCOCK	USA	Biomedical Research and Research Training	001	6	6/29/2010	NON-COMPETING CONTINUATION	$344,520
2010	2009	JACKSON LABORATORY (THE)	600 MAIN STREET	BAR HARBOR	ME	04609	HANCOCK	USA	Biomedical Research and Research Training	000	5	2/22/2010	COMPETING CONTINUATION	$0
														Subtotal = $344,520

Issue Date FY: 2009 ( Subtotal = $348,000 )
2009	2009	JACKSON LABORATORY (THE)	600 MAIN STREET	BAR HARBOR	ME	04609	HANCOCK	USA	Biomedical Research and Research Training	000	5	8/24/2009	COMPETING CONTINUATION	$348,000
														Subtotal = $348,000

Issue Date FY: 2007 ( Subtotal = $320,485 )
2007	2007	JACKSON LABORATORY (THE)	600 MAIN STREET	BAR HARBOR	ME	04609	HANCOCK	USA	Biomedical Research and Research Training	000	4	3/29/2007	NON-COMPETING CONTINUATION	$320,485
														Subtotal = $320,485

Issue Date FY: 2006 ( Subtotal = $330,057 )
2006	2006	JACKSON LABORATORY (THE)	600 MAIN STREET	BAR HARBOR	ME	04609	HANCOCK	USA	Biomedical Research and Research Training	000	3	3/27/2006	NON-COMPETING CONTINUATION	$330,057
														Subtotal = $330,057

Issue Date FY: 2005 ( Subtotal = $338,000 )
2005	2005	JACKSON LABORATORY (THE)	600 MAIN STREET	BAR HARBOR	ME	04609	HANCOCK	USA	Biomedical Research and Research Training	000	2	2/10/2005	NON-COMPETING CONTINUATION	$338,000
														Subtotal = $338,000

Issue Date FY: 2004 ( Subtotal = $331,520 )
2004	2004	JACKSON LABORATORY (THE)	600 MAIN STREET	BAR HARBOR	ME	04609	HANCOCK	USA	Biomedical Research and Research Training	000	1	3/1/2004	NEW	$331,520
														Subtotal = $331,520

Grand Total All Awards = $6,783,456

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Systems Genetic Analysis of Multi-parent Crosses

Award Number: R01GM070683

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/01/2004

PERIOD OF PERFORMANCE END DATE: 07/31/2024

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