Genetic principles Flashcards
What is the difference between somatic cells and gametes?
- Somatic cells are diploid (most body cells)
- Gametes are haploid
What are alleles?
Alternative forms of gene
If a gene displays genetic polymorphism what does this mean?
Genes exist in multiple forms (alleles)
What is the locus (plural loci)?
Location of allele on chromosome
What is the wild type gene/allele?
Gene/allele that is common in most individuals (A in Aa)
What is the difference between a germilne and a somatic mutation?
Germ line
- DNA of sperm/eggs
- Transmitted to offspring
- Found in every cell of the body
Somatic mutations
- Acquired during lifespan of cell
- Not transmitted to offspring
What is codominance?
When both alleles contribute to phenotype
Give a common example of codominance?
Blood groups ABO
AB individuals will express both A and B antigens
What is penetrance?
Proportion with allele that express phenotype
What is incomplete penetrance?
Not all those with disease mutation develop disease
Give an example of a gene mutation which displays incomplete penetrance?
BRCA1 and 2
- Usually Aut dominant disease
What is expressivity?
Variations in the phenotype of gene
What is an example of a disease which displays expressivity?
Neurofibromatosis type 1 (NF1)
- Aut dom
- 100% penetrance
- Extremely variable severity
What is pleiotropy?
One gene which can have multiple different phenotypic effects and traits
- e.g one gene affecting skin, eyes and brain
Give some examples of pleitropy
- PKU - skin, body odor, brain
- Marfan - CV, limbs
- CF - pancreas, lungs
- Osteogenesis imperfecta - eyes, limbs, hearing
What genes are involved in the 2-hit hypothesis?
Tumour suppressor genes
What is the more colloquial term for loss of heterozygosity?
2 hits
- Cancer requiring mutation of both alleles
What percentage of retinoblastoma cases are heriditary?
40%
- Have one gene mutated in all cells at birth (germline mutation)
HNPCC (Lynch syndrome) has a germline mutation in what genes?
Mismatch repair genes
- Example of 2-hit hypothesis
- 1 inherited germline mutation
- 2nd ‘hit’/mutation/inactivation will occur during lifetime -> cancer
What percentage of those with FAP develop colon cancer?
100%
- Prophylactic colectomy
What cancers are those with Li-Fraumeni Syndrome most at risk of?
- Sarcoma
- Breast
- Leukemia
- Adrenal gland
What gene is mutated in Li-Fraumeni syndrome?
TP53
What is mosaicism?
Gene differences in cells of the same individual
What can germline mosaicism appear like?
May appear like a sporadic disease in offspring as it is difficult to detect
- In reality it is germline mosaicism passed down from parent
What is somatic mosaicism?
Gene differences in tissues/organs of an individual that do not involve the germline cells
What diseases may have somatic mosaicism?
- Milder forms of Turner syndrome (45X/46XX)
- Rare forms of Down syndrome (some cells have trisomy 21, others do not)
What syndrome is often used as an example of mosaicism?
McCune-Albright syndrome
What are the features of McCune-Albright syndrome?
- Effects endocrine organs
- Precocious puberty
- Fibrous growth in bones (fractures, deformity)
- Skin pigmentation (Cafe au lait spots. irregular borders)
How early can menstraution occur due to precocious puberty in cafe au lait syndrome?
2 years old
When does the mutation occur in Mccune-Albright syndrome?
- Sporadic mutation in development, after fertilization
- Only some tissues affected, varied presentation due to
- Not inherited from parent
What gene is somatically mutated in McCune Albright syndrome?
GNAS gene
What does GNAS gene code for (McCune-Albright)?
- Alpha subunit of G3 protein
- Activates for adenylyl cyclase
- Continued stimulation of cAMP signaling
Why are germline GNAS mutations never seen?
They are lethal as entire body is affected
Explain genetic heterogeneity?
Same phenotype from different genes/mutations
- Multiple gene mutations often causing the same disease, many diseases have multiple genotypes causing them
What is allelic heterogeneity?
When multiple different alleles can cause the same disease
- However mutation will be found at the same loci
Give 2 examples of diseases which express allelic heterogeneity?
- Beta thalassemia
- Cystic fibrosis
What is locus heterogenity?
When mutations at different loci can cause the same disease
Give an example of a disease which displays locus hetergeneity?
Retinitis Pigmentosum
- X-linked, aut dom and AR forms
- 43 different loci can cause disease
How is retinitis pigmentosum inherited?
Aut dom
