NDLI: Natural selection and mammalian BRCA1 sequences: elucidating functionally important sites relevant to breast cancer susceptibility in humans

Content Provider	Springer Nature Link
Author	Burk Herrick, Angela Scally, Mark Amrine Madsen, Heather Stanhope, Michael J. Springer, Mark S.
Copyright Year	2006
Abstract	Comparison of orthologous gene sequences is emerging as a powerful approach to elucidating functionally important positions in human disease genes. Using a diverse array of 132 mammalian BRCA1 (exon 11) sequences, we evaluated the functional significance of specific sites in the context of selection information (purifying, neutral, or diversifying) as well as the ability to extract such information from alignments that index varying degrees of mammalian diversity. Small data sets of either closely related taxa (Primates) or divergent placental taxa were unable to distinguish sites conserved due to purifying selection from sites conserved due to chance (false-positive rate = 65%–99%). Increasing the number of placental taxa to 57 greatly reduced the potential false-positive rate (0%–1.5%). Using the larger data set, we ranked the oncogenic risk of human missense mutations using a novel method that incorporates site-specific selection level and severity of the amino acid change evaluated against the amino acids present in other mammalian taxa. In addition to sites undergoing positive selection in Marsupialia, Laurasiatheria, Euarchontoglires, and Primates, we identified sites most likely to be undergoing divergent selection pressure in different lineages and six pairs of potentially interacting sites. Our results demonstrate the necessity of including large numbers of sequences to elucidate functionally important sites of a protein when using a comparative evolutionary approach.
Starting Page	257
Ending Page	270
Page Count	14
File Format	PDF
ISSN	09388990
Journal	Mammalian Genome
Volume Number	17
Issue Number	3
e-ISSN	14321777
Language	English
Publisher	Springer-Verlag
Publisher Date	2006-03-03
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Anatomy Zoology Cell Biology
Content Type	Text
Resource Type	Article
Subject	Genetics

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

Genetic mapping of the Brca2 breast cancer susceptibility gene on mouse Chromosome 5

Comparison of the human and murine ATRX gene identifies highly conserved, functionally important domains

Inefficient purifying selection: the mammalian Y chromosome in the rodent genus Mus

Organization and integration sites in the human genome of endogenous retroviral sequences belonging to HERV-E family

AIB1 polymorphisms with breast cancer susceptibility: a pooled analysis of variation in BRCA1/2 mutation carriers and non–carriers

PALB2: a novel inactivating mutation in a Italian breast cancer family

Mammary cancer susceptibility: human genes and rodent models

Mammalian Genome—Looking to the future

Mammalian Genome

Natural selection and mammalian BRCA1 sequences: elucidating functionally important sites relevant to breast cancer susceptibility in humans

Similar Documents

Genetic mapping of the Brca2 breast cancer susceptibility gene on mouse Chromosome 5

Comparison of the human and murine ATRX gene identifies highly conserved, functionally important domains

Inefficient purifying selection: the mammalian Y chromosome in the rodent genus Mus

Organization and integration sites in the human genome of endogenous retroviral sequences belonging to HERV-E family

AIB1 polymorphisms with breast cancer susceptibility: a pooled analysis of variation in BRCA1/2 mutation carriers and non–carriers

PALB2: a novel inactivating mutation in a Italian breast cancer family

Mammary cancer susceptibility: human genes and rodent models

Mammalian Genome—Looking to the future

Mammalian Genome

Natural selection and mammalian BRCA1 sequences: elucidating functionally important sites relevant to breast cancer susceptibility in humans