One of the roles of a population geneticist is to explain the distribution of gene frequencies within and between populations. This approach is broadly employed to address several questions relating to the genetic health of human and non-human populations:
Current research:
Using Multi-Locus Microsatellite Markers to Distinguish Between Inbreeding and Population Substructure.
The British Pakistani Population
The British Pakistani population suffers a ten-fold increase in the incidence of recessive disorders. This observation is frequently explained away by the consanguinity hypothesis: relatives are more likely to carry identical copies of recessive variants, which can result in their offspring inheriting both copies and, subsequently the disorder. However, the Pakistani population is subdivided into biraderi, effectively clans of different sizes. This population substructure substantially complicates genetic analysis. However, the social structure of this population contributes other complicating factors such as endogamous kin-network subdivisions (biraderi). Methods are currently being developed to identify the contribution these subdivisions make to the disease profile of this community.
Group: Andy Overall
Relevant publications: Overall, A.D.J., Ahmad, M., Thomas, M.G., and Nichols, R.A. 2003. An analysis of consanguinity and social structure within the UK Asian population using microsatellite data. Annals of Human Genetics, 67: 525-537.
Overall, A.D.J., Ahmad, M., and Nichols, R.A. 2002. The effect of reproductive compensation on recessive disorders within consanguineous human populations. Heredity, 88: 474-479.
Overall, A.D.J., and Nichols, R.A. 2001. A method for distinguishing consanguinity and population substructure using multilocus genotype data. Molecular Biology and Evolution, 18: 2048-2056.
Related Links: Discussion in the British Medical Journal http://www.bmj.com/cgi/eletters/331/7528/1292#125217
The Genetic Basis of Anxiety: The Renin-Angiotensin System
Anxiety, which accounts for 33% of all major psychiatric disorders in humans, is a complex trait in which the underlying genetics have not yet been characterized. We are currently exploring the use of outbred mice (BKW) as a workable animal model of anxiety-related behaviour in humans. Previous research within the School of Pharmacy and Biomolecular Sciences has characterized the role of the renin-angiotensin system (RAS) in the anxiety-like behaviour of BKW mice. An array of genetic markers is being used to identify any association between the genotype and anxious phenotype.
Group: Paul Gard, Andy Overall, Bruno Golding, Yolande Saab (Lebanese American Univerity)
Relevant Publications: Gard, P.R., Mandy, A., Sutcliffe, M.A. (1999) Evidence of a possible role of altered angiotensin function in the treatment, but not aetiology, of depression. Biological Psychiatry 45 1030-1034.
Gard, P.R., Haigh, S.J., Cambursano, P.T., Warrington, C.A. (2001) Strain differences in the anxiolytic effects of losartan in the mouse. Pharmacol. Biochem. Behav. 69, 35-40.
Saab YB, Gard PR, Haddad R, Khabbaz R, Ali A, Overall ADJ. The association of hypertension with renin-angiotensin system polymorphisms in the Lebanese population (in prep).
Saab YB, Gard PR, Overall ADJ. The geographic distribution of the ACE II genotype: A novel finding (in prep).
The Role of N-methyl-D-aspartate (NMDA) Receptor Genes in Smoking Behaviour.
Lack of impulse control is thought to be a major factor in drug taking behaviour (addiction) and to contribute to relapse in former addicts. Recently, greater trait impulsivity has been reported to predict relapse in former smokers. Pre-clinical studies using antagonists at the NMDA receptor indicate that glutamate plays a role in impulse control and in humans distinct polymorphisms of the NMDAR2B subunit are found in Type 2 alcoholics – Type 2 alcoholics show greater impulsivity than Type 1.
Taken together, the above evidence suggests that polymorphisms in the NMDAR2 subunit gene may be markers of the predisposition of smokers to the degree of impulse control problems that they might experience during abstinence. We are currently exploring the association between NMDAR2 polymorphisms and impulsive responding in healthy human smokers during abstinence.
Group: Anne Jackson, Andy Overall.
