Genetics Flashcards
- Huntingtons disease, Marfans syndrome and Achondroplasia
- An affected person has at least one affected parent.
- Affects either sex.
- Transmitted by either sex.
- A child of an affected X/ unaffected mating has a 50% chance of being affected (this assumes that the affected person is heterozygous, which is usually true for rare conditions).
- Only one bad gene is required to give the effect
most dominant diseases are caused by the production of a “poison” product, an abnormal product or waste accumulation. in their presence the normal gene cannot compensate
in order for these genes to be maintained within a population the diseases must be passed on- late onset e.g. huntingtons, reduced penetrance, variable expressivity.
Autosomal Dominant
Cystic Fibrosis, sickle cell disease, Thalassaemias. PhenylPKU
- Affected people born to unaffected parents.
- Parents usually asymptomatic carriers.
often increased incidence of parental consanguinity.
- Affects either sex.
- only affects homozygote
- result in a decrease in the levels or activities of proteins.
- Heterozygotes may have half the protein or activity of “normals” and be clinically unaffected. In some diseases e.g. haemoglobinopathies heterozygotes may show mild symptoms
Autosomal recessive
2 carrier parents have 25% chance affected child.
Consanguinity ^ chance
Inborn errors of metabolism normal AR. Error in a gene coded for an enzyme
- Hemophila, colour blindness, muscular dystrophy
- Affects almost exclusively males.
- Affected males are usually born to unaffected parents; the mother is normally an asymptomatic carrier and may have affected male relatives.
- Females may be affected if the father is affected and the mother is a carrier, or occasionally as a result of non-random X-inactivation.
- There is no male-to-male transmission in the pedigree (but matings of an affected male and carrier female can give the appearance of male-to-male transmission.
X-linked
Somatic and germ line cells
Somatic cell mutations not passed on to children
Germ line cells may be.
Monosomy
One copy of chromosome
Monosomy X
Turners syndrome
Only females
Trisomy
Three copies of a chromosome
Trisomy 21 - downs syndrome
Trisomy 13 - Patau syndrome
Trisomy 18 - Edwards syndrome
Triploidy
three sets of genetic material - no live births
Nondisjunction
The abnormal distribution of chromosomes during meiosis ending up with double of nothing.
Mutation
A permanent change in DNA sequence.
Large scale: Chromosomal level) - gain/loss of chromosomal regions
Translocations of parts of a chromosome.
Small Scale Mutations: (DNA level)
Nucleotide base substitutions, deletions, or insertions.
Missense mutation
result in an amino acid substitution
Nonsense mutation
result in the premature addition of a stop codon
Frameshift mutation
result in an alteration of the reading frame, and thus an alteration to the amino acid sequence.
Triplet repeat mutation
expand a critical area of a gene and subsequently alter the structure of a protein
Point mutation
These are changes in single bases within the gene, they may or may not change the encoded amino acid and the effect is variable e.g. sickle cell disease and ABO blood groups are the result of point mutations. Many diseases are caused by point mutations and these are difficult to detect by molecular technologies
NZ New Born screening program
Phenylketonuria (PKU) Cystic Fibrosis (CF) Biotinidase Deficiency Congenital Adrenal Hyperplasia (CAH) Galactosaemia Hypothyroidism Maple Syrup Urine Disease (MSUD)
Prenatal tests
Give an estimate of the chance a disorder will occur
Identify women < 35 years old with higher risk pregnancies who can be offered diagnostic testing
Less invasive than diagnostic testing
Not a “Yes” or “No” answer
False +, False -
Nuchal Translucency Screen
Ultrasound performed at 11-14 weeks gestation
Measurement of the thickness of the fluid that accumulates under the skin at the back of the neck
Increased Nuchal Translucency is associated with an increased chance of Down Syndrome
Maternal Age + Gestational Age + Nuchal Measurement into computer algorithm to produce an estimated risk for Down Syndrome
Maternal Serum Screen
Maternal blood test at 15-17 weeks gestation
Measures the level of 3 proteins produced by the fetus & placenta
Maternal age + Protein levels are combined to produce an estimated risk for Chromosome Abnormalities and Neural Tube Defects
Not applicable for a diabetic mother, or a multiple pregnancy
Costs $75
Detailed Prenatal Ultrasound
Both a screening test and a diagnostic test
Screening
◦Ultrasound findings which increase the chance that the fetus has a chromosome problem
◦e.g. shortened femur, nuchal oedema
Diagnosis
◦e.g. identification of Achondroplasia, NTD
Prenatal Tests - Diagnostic
Give a clear answer (usually) about whether or not the fetus has a particular condition
Provide the most accurate results
Involve invasive procedures which carry a risk of miscarriage
Are only routinely offered to those at higher risk
e.g. women >35 yrs
women with an “increased risk” result on a screening test
significant family history
Amniocentesis
Performed after 14 weeks of gestation
Karyotype from a sample of amniotic fluid
Identifies major chromosome anomalies
Does not identify gene mutations, very small chromosome changes, or structure and development of the fetus
Risk of miscarriage associated with the test is 1/200
Chorionic Villus Sampling (CVS)
Performed between 10-12 weeks of gestation
Karyotype analysis from a sample of the placenta
Identifies major chromosome anomalies
Does not identify gene mutations, very small chromosome changes, or structure and development of the fetus
Risk of miscarriage associated with this test is 1/100
Pregnancy screening results
Amniocentesis ~ 99.5% accurate CVS ~ 96% accurate Errors in result can arise from: ◦Culture failure ◦Maternal Cell Contamination ◦Mosaicism - sample has a mixture of normal and abnormal cells
