Lecture 13 - Human genetics Flashcards
(20 cards)
Describe genetic degeneracy
Occurrence of ‘silent’ variants
What are alleles
Different forms of the same gene or genetic locus
What is polymorphic loci
Several different alleles - no variation from person to person
Describe a genetic marker
Variable providing information on specific DNA sequence at particular locus
Describe disease susceptibility locus
Causal for particular disease
How do genetic variants arise
DNA undergoes frequent chemical change - when replicated - most quickly repaired
Mutation is a failure of DNA repair
Are mutations beneficial or harmful
No effect (neutral)
Beneficial
Harmful
What is the difference between variants and mutations
Mutation - restrictive way - known genetic marker of disease or associated with susceptibility to disease
A new genetic variant created by mutation during replication or reproduction
What are SNPs
Single Nucleotide Polymorphisms
-Base substitutions (NOT changes in # or arrangement)
Most common - unique genomic sequence arrangement for individuals
- No typically disease associated
What is a DNA haplotype
Group of SNPs and genes inherited together from single parent
haplotype represents individuals combination of SNPs and gene - rarely separated by recombination (close proximity)
What are the different types of point mutations
Silent - synonymous
Missense - (non-synonymous) - conservative (similar chemistry) - non-conservative
Nonsense - (premature stop)
What is sickle cell disease
Non-conservative missense in beta-globin gene (HBB)
What are the consequences of point mutations
Outside of gene have little to no effect on protein production or function
Non-coding - change amount of protein produced
coding region - change amino acid sequence
Describe frameshift mutations
Insertion/deletion (InDel) - disrupt codon grouping -> completely different protein translation
- altered reading frames (stop codon -> loss of protein function)
- multiples of 3 BP causes no loss or gain of codons and corresponding acids
What is an example of a frame shift mutation
Tay Sachs Disease
- inherited autosomal recessive
- progressively destroys nerve cells in brain and SC
- caused by frameshift mutations in HEXA gene
What are copy number variations (VNTRs)
Variable number of tandem repeats or shot tandem repeats - minisatellites
What is an examples of copy number variations
Huntington’s disease - excessive repetitions of cytosine-adenine-guanine nucleotide sequence
Describe translocation
Movement on DNA stretch to new non-homologous chromosomal location (no molecular loss)
Genes at or near fusion boundaries become disrupted - result in formation of functionally fused abnormal gene products (‘chimeric proteins’)
What is an example of translocation
Philadelphia chromosome
- Chronic Myeloid Leukaemia’s (CML)
- Produce BCR-ABL fusion protein
- Changes localisation of ABL kinase form nucleus to cytoplasm
activation of abnormal proliferation and survival pathways
Describe nondisjunction
Failure of chromosomes to segregate correctly - too many or too few chromosomes
