Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Apr;52(4):224-30.
doi: 10.1136/jmedgenet-2014-102766. Epub 2015 Feb 2.

BRCA1 Circos: a visualisation resource for functional analysis of missense variants

Ankita Jhuraney  1 , Aneliya Velkova  2 , Randall C Johnson  3 , Bailey Kessing  3 , Renato S Carvalho  4 , Phillip Whiley  5 , Amanda B Spurdle  5 , Maaike P G Vreeswijk  6 , Sandrine M Caputo  7 , Gael A Millot  8 , Ana Vega  9 , Nicolas Coquelle  10 , Alvaro Galli  11 , Diana Eccles  12 , Marinus J Blok  13 , Tuya Pal  14 , Rob B van der Luijt  15 , Marta Santamariña Pena  16 , Susan L Neuhausen  17 , Talia Donenberg  18 , Eva Machackova  19 , Simon Thomas  20 , Maxime Vallée  21 , Fergus J Couch  22 , Sean V Tavtigian  23 , J N Mark Glover  10 , Marcelo A Carvalho  4 , Lawrence C Brody  24 , Shyam K Sharan  25 , Alvaro N Monteiro  14 ; Evidence-based Network for the Interpretation of Germline Mutant Alleles Consortium
Affiliations

BRCA1 Circos: a visualisation resource for functional analysis of missense variants

Ankita Jhuraney et al. J Med Genet. 2015 Apr.

Abstract

Background: Inactivating germline mutations in the tumour suppressor gene BRCA1 are associated with a significantly increased risk of developing breast and ovarian cancer. A large number (>1500) of unique BRCA1 variants have been identified in the population and can be classified as pathogenic, non-pathogenic or as variants of unknown significance (VUS). Many VUS are rare missense variants leading to single amino acid changes. Their impact on protein function cannot be directly inferred from sequence information, precluding assessment of their pathogenicity. Thus, functional assays are critical to assess the impact of these VUS on protein activity. BRCA1 is a multifunctional protein and different assays have been used to assess the impact of variants on different biochemical activities and biological processes.

Methods and results: To facilitate VUS analysis, we have developed a visualisation resource that compiles and displays functional data on all documented BRCA1 missense variants. BRCA1 Circos is a web-based visualisation tool based on the freely available Circos software package. The BRCA1 Circos web tool (http://research.nhgri.nih.gov/bic/circos/) aggregates data from all published BRCA1 missense variants for functional studies, harmonises their results and presents various functionalities to search and interpret individual-level functional information for each BRCA1 missense variant.

Conclusions: This research visualisation tool will serve as a quick one-stop publically available reference for all the BRCA1 missense variants that have been functionally assessed. It will facilitate meta-analysis of functional data and improve assessment of pathogenicity of VUS.

Keywords: BRCA1; Cancer: breast; Clinical genetics; Molecular genetics.

PubMed Disclaimer

Figures

Figure 1
Figure 1
BRCA1 Circos excluding exon 11. (A) BRCA1 Circos with no data on display for exon 11 to facilitate data visualisation for the remaining exons (see figure 2 for BRCA1 Circos including exon 11 data). All documented BRCA1 missense variants are represented in the Circos plot that contains 53 concentric tracks (left panel). (B) Magnified view of the region depicted in the inset (dashed lines) from (A). Refer to table 1 for detailed descriptions of each track. BRCA1 Circos can be accessed via the website http://research.nhgri.nih.gov/bic/circos/ with mouse-over and search functionalities.
Figure 2
Figure 2
BRCA1 Circos including exon 11. All documented BRCA1 missense variants are represented in the Circos plot that contains 53 concentric tracks. Refer to table 1 for detailed descriptions of each track. BRCA1 Circos can be accessed via the website http://research.nhgri.nih.gov/bic/circos/ with mouse-over and search functionalities.
Figure 3
Figure 3
Zooming in on an individual variant. A sample section of the BRCA1 Circos representing two missense variants, M1775K and M1775R, is shown. Each variant should be read radially to get information on all the tracks for the each variant. Refer to table 1 for detailed descriptions of each track. BIC, Breast Cancer Information Core; GVGD, Grantham Variation-Grantham Deviation; IARC, International Agency for Research on Cancer.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Claus EB, Risch N, Thompson WD. Genetic analysis of breast cancer in the cancer and steroid hormone study. Am J Hum Genet 1991;48:232–42. - PMC - PubMed
    1. Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 1994;266:66–71. 10.1126/science.7545954 - DOI - PubMed
    1. Tavtigian SV, Simard J, Rommens J, Couch F, Shattuck-Eidens D, Neuhausen S, Merajver S, Thorlacius S, Offit K, Stoppa-Lyonnet D, Belanger C, Bell R, Berry S, Bogden R, Chen Q, Davis T, Dumont M, Frye C, Hattier T, Jammulapati S, Janecki T, Jiang P, Kehrer R, Leblanc JF, Mitchell JT, McArthur-Morrison J, Nguyen K, Peng Y, Samson C, Schroeder M, Snyder SC, Steele L, Stringfellow M, Stroup C, Swedlund B, Swense J, Teng D, Thomas A, Tran T, Tranchant M, Weaver-Feldhaus J, Wong AK, Shizuya H, Eyfjord JE, Cannon-Albright L, Labrie F, Skolnick MH, Weber B, Kamb A, Goldgar DE. The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds. Nat Genet 1996;12:333–7. 10.1038/ng0396-333 - DOI - PubMed
    1. Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C, Micklem G. Identification of the breast cancer susceptibility gene BRCA2. Nature 1995;378:789–92. 10.1038/378789a0 - DOI - PubMed
    1. Mavaddat N, Peock S, Frost D, Ellis S, Platte R, Fineberg E, Evans DG, Izatt L, Eeles RA, Adlard J, Davidson R, Eccles D, Cole T, Cook J, Brewer C, Tischkowitz M, Douglas F, Hodgson S, Walker L, Porteous ME, Morrison PJ, Side LE, Kennedy MJ, Houghton C, Donaldson A, Rogers MT, Dorkins H, Miedzybrodzka Z, Gregory H, Eason J, Barwell J, McCann E, Murray A, Antoniou AC, Easton DF; EMBRACE. Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE. J Natl Cancer Inst 2013;105:812–22. 10.1093/jnci/djt095 - DOI - PubMed

Publication types