Common Diseases

Common disease = disease in >1 in 1000 of population e.g. diabetes, cancer, inflammatory bowel diseaseNon-mendelian inheritanceEvidence that a disorder is genetic - twin/adoption studies, familial clustering, increased incidence in certain ethnic groups e.g. jewish population (2-4x greater risk of inflammatory bowel disease), migration studies (although ethnic group has migrated ie. different environment, still high incidence of the disease), animal models of disease e.g. agouti obese mouseWhy perform genetic investigations into common disease?Treatment - understand pathogenesisPrevention - pharmacogeneticsMonogenic disorder can aid our understanding of common disorders  

Individuals with mutation in the FLG gene - encoding fillagrin - are much more likely to develop ichthyosis vulgaris (extremely dry skin), eczema, asthma, hay fever, peanut allergy 1 in 250 people have ichthyosis vulgaris 10% of all europeans are heterozygous for a truncating mutation in the gene causing loss of function Semi-dominant pattern of inheritance - if you have too mutated alleles - more severe disease   Many different mutations - some are common in europeans, others are common in asians

ob/ob mouse is leptin deficientRare CNVs cause leptin deficiency in humans

Intro

Fillagrin

Leptin