Where adult tissue is damaged, a complex repair process is taking place involving regeneration and acute phase immunological response. Unlike embryonic tissues, adult repair always leads to the formation of a fibrotic scar where the wound has healed, which ultimately can disable proper tissue function [1]. In recent years, research was able to link several genes to the event of scar formation . Knockdown of Ostepontin (OPN) in mice for example resulted in reduced granulation tissue formation and scarring [2]. It also has been indicated that TGF-beta1 in conjunction with Connective tissue growth factor (CTGF) is promoting scar formation [3]. Most of this data comes from mouse model studies, in humans however, less is known.

BCG injections were routinely given in schools since the 1960s (up until 2005) and lead to a charateristic scar, which individually differs in size and character. Before injection, a skin test is performed to test for exsiting Tuberculosis antibodies. If the test is negative, BCG injections are given [4,5]. In the age group of ALSPAC mothers, up to 70% were immunised each year during childhood, making it a great read-out for assessing population wide scarring outcomes.

By collecting information about different levels of BCG scarring outcomes in ASLPAC mothers by telephone interviews and combining this data with genome data we hope to perform a genomewide associaiton study (and possible rare variant analysis) for scar type. For ethical approval this research proposal will be submitted to ALEC. Please find attached documents summarising the infornation and SOP to be summarised and used during the course of proposed telephone interviews. These are in the process of development before submission to ALEC.

Analysis plan:

(i) develop cover letter, info sheet, protocol and consent form for the BCG scar study for use within a telephone interview

(ii) submitt proposal to ALEC for ethical approval

(iii) collect phenotypic data - coordinated effort with Kate Sherlock and tele-contact team

(iv) submit data for processing by ALSPAC team

(v) unite both genetic and phenotypic data to undertake tests of association

between genetic variation and phenotypic characterisation.

(vi) test selected genes plus surrounding regions locally for variant associated with scarring outcome

Genetic analysis will be supported by Nic Timpson.

1. Stramer, B.M., R. Mori, and P. Martin, The inflammation-fibrosis link? A Jekyll and Hyde role for blood cells during wound repair. J Invest Dermatol, 2007. 127(5): p. 1009-17.

2. Mori, R., T.J. Shaw, and P. Martin, Molecular mechanisms linking wound inflammation and fibrosis: knockdown of osteopontin leads to rapid repair and reduced scarring. J Exp Med, 2008. 205(1): p. 43-51.

3. Shi-Wen, X., A. Leask, and D. Abraham, Regulation and function of connective tissue growth factor/CCN2 in tissue repair, scarring and fibrosis. Cytokine Growth Factor Rev, 2008. 19(2): p. 133-44.

4. NHS (1996) Immunisation against infectious disease - The green book 1996 edition.

5. Shaaban, M. A., Abdul Ati, M., Bahr, G. M., Standford, J. L., Lockwood, D. N. and McManus, I. C., Revaccination with BCG: its effects on skin tests in Kuwaiti senior school children. Eur Respir J, 1990. 3(2): 187-91.