Human genetics 2

disease due to recessive gene

PKU, sickle-cell anemia, tay-sachs, cystic fibrosis

disease by dominant gene

huntington’s disease, neurofibromatosis

disease by polygenic inheritance

cancer, heart disease, asthma, psychiatric and behavioural disorders

diseases from sex-linked inheritance

red-green colour blindness, hemophilia, duchenne muscular dystrophy, fragile-X-syndrome

diseases from chromosomal anaomalises

down syndrome, klinefelter syndrome and turner syndrome (OX)

tay-sachs disease

fatal neurodegenrative disease in infancy and early childhood. caused by mutation of HEXA gene on chromosome 15q23-q24

• infants develop normally until 3-6 months

• no cure or treatment

• autosomal and recessive

huntington’s disease

progressive neurodegenerative disroder. gene on chromosome 4p16.3 with 40+ repeat of CAG codons

• autosomal dominant

• mean onset 40 years and death 12-15 yrs after

• onset appears earlier when from father

physical symptoms of huntington’s disease

• voluntary movement - Bradykinetic (slowness), Akinesia (freezing), uncoordinated

• involuntary - chorea (involuntary jerking), dystonia (muscle contractions

• neuronal and astrocyte loss in basal ganglia and as disease progresses greater cortical atrophy

potential treatment of huntington’s

AMT-130 gene therapy targeting striatum - delivers genetic material that reduces production of toxic huntingtin protein

• 75% slowing of disease at 3 years post treatment

fragile-X syndrome

most common inherited intellectual disability. abnormal gene on X (sex-linked). expansion mutation of CGG repeat sequence in FMR1 gene at Xq27.3 = silences gene causing absence of FMR1 protein

• normal have <55 CGG repeat

• carriers 55-200 repeats

• fragile X 200+

FMR1 protein

essential for brain development incl brain synaptic plasticity, development of shape and cog dev

polygenic transmission

traits controlled by 1+ genes e.g. height and behavioural traits like intelligence and depression

schizophrenia

distortions of thinking and perceptions, psychopathological thoughts = sig social and occupational dysfunction

• onset young adulthood

• continuous or episodic

• not due to other mental disorders or substance abuse

• likely polygenic genetic risk

phenylketonuria (PKU)

unable to metabolise phenylalanine = builds up in body causing brain developmental problems

• autosomal recessive - defective gene on chromosome 12

• mental retardation can be avoided with early diagnosis and restricted dieat

• phenylalanine - amino acid in high protein foods

range/norm of reaction

all phenotypes that could theoretically result from a given genotype, given all the environments in which it could survive and develop

genome

complete set of genetic material of an organism

epigenome

complete set of chemical changes to DNA and histone proteins

• doesn’t invole changes to DNA sequence

epigenetic changes

heritable but reversible changes in gene expression thats not coded in DNA sequence

• post-translational changes

3 mechanisms for gene regulation

histone modification, DNA methylation and microRNA

autoimmune disease

immune system attacks own body

• monozygotic twin studies show differences suggesting role of environmental factors in disease development