The human genome Contains all the genetic material of an individual Made up of DNA Determines structure and function Is inherited from our parents

Series of nucleotides (bases) A, G, C, T Organization: genes <2.0% of genome 20 000 genes other regions

Variants/mutations We inherit hundreds of variants/mutations from our parents The DNA in our own cells acquires several new variants/mutations during a lifetime Causes environment – majority cell division (DNA duplication)

6 × 109 base pairs of DNA need to be replicated, packed and segregated every time a cell divides Repeated up to a trillion (1012) times during the development of a human from a fertilized egg

Human genetic disorders Monogenic disorders Rare > 10 000 known (WHO) Collectively occur in 1:200 individuals Examples Cystic fibrosis Muscular dystrophy Sickle cell anaemia Osteogenesis imperfecta Neurofibromatosis

Human genetic disorders Polygenic/multifactorial disorders Common Important environmental component Examples Heart disease Atherosclerosis Cancer Obesity Diabetes Hypertension Autoimmune disease

Types of monogenic disorders Recessive or dominant disorders Autosomal or sex-linked disorders

Monogenic (single gene) disorders: autosomal recessive Examples cystic fibrosis sickle-cell anemia oculocutaneous albinism phenylketonuria Two mutated alleles i.e. one from each parent

Monogenic (single gene) disorders: autosomal dominant Examples myotonic dystrophy familial hypercholesterolemia neurofibromatosis polycystic kidney disease Huntington’s disease One mutated allele i.e. from either parent

Monogenic (single gene) disorders: sex-linked Recessive Hemophilia, Duchenne muscular dystrophy Usually affects men Dominant Very rare: hypophosphatemic rickets, Rett syndrome Y-linked Only in males Neither dominant or negative since only one allele

Penetrance The proportion of individuals carrying a particular mutation that express an associated phenotype e.g. 95% penetrance: 95% of individuals with the mutation will develop the disease, while 5% will not Causes of variation in penetrance Age Environmental modifiers Genetic and epigenetic modifiers

Gaussian distribution “Bell-shaped” curve Individual molecule (e.g. enzyme) Structure/function

Normal distribution and standard deviation For the normal distribution, one standard deviation, this accounts for about 68% of the set, while two standard deviations from the mean account for about 95%, and three standard deviations account for about 99.8%

Body height and weight Number of people Height (cm) Weight (kg)

Skin colour Number of people Pigmentation (skin colour)

Blood cholesterol levels Number of people Cholesterol

HIV/AIDS Adult-onset diabetes Cystic fibrosis Genetic component Environmental component http://science.education.nih.gov/supplements/nih1/genetic/guide/genetic_variation2.htm