Germ cells, somatic cells, mitosis, meiosis
Down`s, Klinefelter, XXY, Turner, X0
Adenine, thymine, guanine, cytosine
Triplet code, amino acids, proteins
Somatic cell mutation, germ line mutation
Patterns of inheritance
Polygenic, type 2 diabetes
Monogenic, familial hypercholesterolaemia
Mutations and cancer
Carcinogens cause mutations.
Cancer tissues are clonal, but further mutations do occur, multistep carcinogenesis.
Initiator, promoter, complete carcinogens, incomplete carcinogens.
Proto-oncogenes may mutate into oncogenes by the process of onchogenesis
Intrinsic and extrinsic oncogenes.
Tumour suppressor genes may mutate to lose function, e.g. retinoblastoma, familial adenomatous polyposis, neurofibromatosis, BRCA 1, BRCA 2.
BRCA mutation give an 85% of breast and 60% chance of ovarian cancers.
Genetic mutation of the FAP dominant gene causes 1% of CRC cases, carriers have an almost 100% chance of developing the disease by 40 years. The mutated FAP gene is also seen in most sporadic colon adenomas and carcinomas. The mechanism of action is a reduced susceptibility to apoptosis.
DNA repair genes may be mutated.
Carry a mutation in a particular oncogenes, but often a second `hit` is needed, the 2 hit model.
Hereditary non-polyposis colorectal cancer (HNPCC) causes 10 – 30% of colorectal carcinoma, mostly involving autosomal dominant genes hMLH1 and hMSH2.
In HNPCC there is more endometrial, gastric, biliary tract, urinary tract, ovarial and small bowel malignancies.
HNPCC families have defective DNA repair enzymes so accumulate mutations at a faster rate.
Zygote - embryo - fetus
Teratogens, infectious agents, chemicals and drugs, radiation, malnutrition
Abnormal embryologic development
Patent ductus arteriosus
Bad start thinking
Many new developments in genetics have ethical implications
Detection of carriers
Three parent babies (for mitochondrial diseases)
Prenatal diagnosis (embryo selection)
Somatic gene therapy
Germ line gene therapy
Stem cells – unipotnet, pluripotent, multipotent
Auto stem cells
Donor stem cells
Human genome project
Gene for criminality, intelligence, aggression
Right to know / not to know
Dilemmas over treatments after diagnosis – patient’s best interests v scientific progress
Diagnosis of sex
Obtain a full history
Establish an accurate diagnosis
Draw a family tree, circles for females, squares for males
Estimate risk of carrying a disorder
Information empowers the individual
Possibilities of future children being affected
Informed choices about their lives
We do not make these choices on behalf of an individual.
Empathise regarding feelings
Right to know, or not
Continued support and follow-up