Genetics Flashcards
Causes of disease x 3
Genetic - Down syndrome, Huntington, Cystic Fibrosis etc
Multifactorial - Cleft lip, diabetes, Heart disease (due to a mix of genetic and environmental factors)
Environmental - Diet, Drugs, infection
Definitions: Genotype Phenotype Allele Polymorphism Homozygous Heterozygous Hemizygous
Genotype - genetic makeup of an individual
Phenotype - appearance/physical characteristics (mix of environment and genes)
Allele - Alternative form of a gene
Polymorphism - DNA sequence variation
Homozygous - both alleles the same
Heterozygous - alleles at the locus are different
Hemizygous - only 1 allele present at the locus
Classification of genetic diseases:
Chromosomal:
- change in the structure or number of chromosomes
Mendelian:
- disorder due to alteration in one gene - AD, AR, SD, SR
Non Mendelian:
- imprinting/epigenetics
- Mitochondria mutations
- Mosaicism
Mitochondria DNA
Ring of DNA used to produce proteins for the mitochondria
Mitochondria are mostly from your mum as many more fir in the egg cell - hence condition will be passed on via women
De novo mutation
A mutation that happens in the sperm or egg cell and can be passed on to offspring
Translocation chromosome variation
Chromosome breaks and a portion reattaches to another chromosome.
Reciprocal = no genetic material lost - not effect parent but may effect offspring
Robertsonian = long arms of 2 chromosomes fuse to form 1, short arm is lost and hence there is a loss of genetic material
Inversion chromosome variation
c/some breaks and a section joins reversed.
Paracentric doesn’t include the centromere
Pericentric does
Deletion chromosome variation
Deletion of a single base to a large piece of chromosome during DNA replication.
Interstital = in middle of the chromosome
Terminal = on the end
Duplication chromosome variation
Production of one or more copies of a gene, part or whole chromosomes.
Tandem = same way Inverted = added on in reverse
Ring chromosome
When the ends of a c/some becomes deleted the ends may join to form a ring.
Fragile site
Part of the chromosome that may break when exposed to partial replication stress.
Autosomal recessive inheritance
Only shown in heterozygous state
Male and female affected in equal proportions
Uncommon in pedigree with few individuals affected
To work out the risk factor of a baby having a genetic disease…
Chance carrier x chance carrier x risk of child affected if both carriers
Definitions: Autosome Allelic heterogeneity Consanguinity Autozygosity Penetrance Expressivity Anticipation
- Any chromosome other than the sex chromosomes
- Situation where different mutations result in the same genetic condition
- Reproductive union between 2 relatives
- Homozygosity by descent - inheritance of same allele through two branches of the family
- % of individuals with a specific genotype showing the expected phenotype
- Refers to the range of phenotypes expressed by a specific genotype
- Where by genetic disorder affects successive generations earlier and more serve - usually due to expansion of triplet repeat
Autosomal Dominant inheritance
Male and female affected in equal proportions
In multiple generations and more common than recessive
Somatic mosaicism
Genetic fault in some tissues of the body
E.g. cancer that develops only in some certain tissues.
Gonadal mutation
Genetic fault present in gonadal tissue
As it is present in germ cells it develops into all cells and hence can be passed on.
X linked inheritance
Usually only males affected
Not passed from males to males as X chromosome is responsible.
Lyonization
Generally only 1 of 2 chromosomes active in each female cell as only one lot of product is needed. Which cell is activated can be switched .
Mitochondria DNA
Mostly inherited from mother
Homoplasmy = a eukaryotic cell whose mitochondrial DNA copies are identical
Heteroplasmy = multiple copies of mtDNA in each cell, with only a proportion being affected by a mutation. Level of severity can vary.
Most Mt diseases are caused by DNA in the nucleus (85%)
Variant
Nucleotide sequence of the gene varies of that from from the normal population
Incidental/secondary findings
Additional findings concerning a patient that may or may not have potential health implications. They are discovered during the genetic test, but are beyond the aims of the original investigation.
E.g - non paternal discovery, risk of early onset of…
Important to have full conscientious before the investigation takes place
Sequencing DNA - Sanger
Uses PCR to amplify regions of interest followed by sequencing of products. Useful for a single gene test.
Time consuming and expensive, but very accurate
NGS - next generation sequencing
Massively parallel sequencing
Low cost per gene
Very fast
But less accurate and a huge about of raw data
Interpretation
Genes vary from Normal — variant of unknown significance — pathogenic variant
If the variant is unknown we can compare it to a healthy control population, check it against the healthy family members.
If a.a change is significant e.g charge polarity etc then we can predict the variation will be pathogenic.
Wild type variant
The normal variant
RNA sequencing
Can be used to analyse transcriptome and hence detect if a variant produces a non functioning protein and hence the severity of its impact.
Ideogram:
Diagram showing expected chromosome banding after G staining
