Genetics

 

 

Cells

Germ cells, somatic cells, mitosis, meiosis

 

 

 

Mutation

Chromosome mutation

Homologous chromosomes

Down`s, Klinefelter, XXY, Turner, X0

 

Gene mutation

Adenine, thymine, guanine, cytosine

Triplet code, amino acids, proteins

Somatic cell mutation, germ line mutation

Mendelism, Lamarkism

 

 

 

Patterns of inheritance

Polygenic, type 2 diabetes

Monogenic, familial hypercholesterolaemia

Autosomal dominant

Autosomal recessive

Sex-linked

 

 

 

Disease aetiology

Environmental aetiology

Genetic aetiology

 

 

 

Mutations and cancer

Carcinogens cause mutations.

Cancer tissues are clonal, but further mutations do occur, multistep carcinogenesis.

Initiator, promoter, complete carcinogens, incomplete carcinogens.

 

 

Cancer

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.

 

 

Cancer families

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.

 

Terms used in genetics

 

Allele

 

Chromosome

 

Deoxyribonucleic acid

 

Diploid

 

Dominant

 

Gamete

 

Genotype

 

Haploid

 

Heterozygous

 

Homologous chromosome

 

Homozygous

 

Linkage

 

Sex linkage

 

Meiosis

 

Mitosis

 

Ovum

 

Phenotype

 

Recessive

 

Zygote

 

 

Congenital malformations

 

Zygote - embryo - fetus

 

Teratogens, infectious agents, chemicals and drugs, radiation, malnutrition

 

Abnormal embryologic development

 

Club foot

 

Hip dislocation

 

Spina bifida

 

Anencephaly

 

Hypospadis

 

Patent ductus arteriosus

 

Cleft lip

 

VSD ASD

 

Bad start thinking

 

New developments in genetics

 

 

Many new developments in genetics have ethical implications

 

 

Prenatal testing

 

 

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

 

 

Cloning

 

 

Therapeutic cloning

 

 

Human genome project

 

 

Positive eugenics

 

 

Negative eugenics

 

 

Bespoke pharmacy

 

 

Genetic engineering

 

 

Transgenic organisms

 

 

DNA fingerprinting

 

Gene for criminality, intelligence, aggression

 

Life insurance

 

Right to know / not to know

 

Dilemmas over treatments after diagnosis – patient’s best interests v scientific progress

 

Animal transplantation

 

Diagnosis of sex

 

Transsexualism

 

 

Genetic counselling

 

   

 

Obtain a full history

 

 

 

Establish an accurate diagnosis

 

 

 

Draw a family tree, circles for females, squares for males

 

 

 

Estimate risk of carrying a disorder

 

 

 

How transmitted

 

 

 

Information giving

 

 

 

Health educator                        

 

 

 

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

 

 

 

Genetic screening