mendelian inheritance of human disease Flashcards
what are the 5 types of mutation?
- Base change causing amino acid change (missense)
- Base change causing premature stop
- Insertion or deletion of bases “in frame”
- Insertion or deletion of bases out of frame
- Mutations affecting promotors or splicing
what are 3 mendelian inheritance mutations which cause disease?
- Autosomal dominant - passed on through generations
- Autosomal recessive - passed on through gen but not necessarily expressed
- X-linked
- Mitochondrial
packaging of DNA:
what is a chromosome?
what is a gene?
what is a locus?
what is an allele?
- chromosome = linear DNA molecule
- gene = length of DNA which encodes a particular protein
- locus = genes are arranged along the chromosome in a linear order, with each gene in a precise location
- allele = alternative forms of a gene, varying in each individual
- each chromosome bears only a single allele at a given locus
how man chromosomes does a human have?
- Human = 46 chromosomes = 2x23 homologous pairs
- in females = 2x22 and XX
- in male = 2x22 pairs and XY
what is a genetic disease?
what are 5 examples of changes in DNA sequences?
Genetic disease - a disease caused by changes in the DNA sequences (genes)
- chromosome aneuploidies (extra or missing chromosome)
- more subtle chromosome abnormality (deletion/moving of locus)
- extra piece of chromosome
- missing piece of chromosome
- change in gene sequence:
- insertion/deletion of bases/change of single base
where and when can mutations occur?
mutations can occur anywhere and could change information flow and cause a deleterious effect:
- DNA is the whole genetic information
- Transcription - converting DNA to mRNA
- Translation - converting mRNA into proteins
mutations and their effects:
what do promoter and splice site sequence changes effect?
- Promotor and splice site sequence changes:
- Stops transcription or causes abnormal splicing
mutations and their effects:
what do base changes which cause an amino acid change (missense) cause?
- Base change causing an amino acid change: (missense)
- Causes change in protein sequence
- Not every base change causes disease (not all deleterious)
- This may or may not reduce protein function
- Some missense mutations make a protein work faster (advantageous)
- base change causing a premature stop codon
mutations and their effects:
what can the insertion or deletion of bases cause?
- Insertion or deletion of bases:
- remember that 3 base pairs encode 1 amino acid
- Mutations may be “in-frame” or “out of frame”
what is a trinucleotide repeat expansion?
the replication of a trinucleotide
what is mendelian inheritance?
what is non-mendelian inheritance?
Mendelian Inheritance: a change in a single gene, sufficient to cause clinical disease, is inherited in a fashion predicted by Mendel’s laws
everything else including common “multifactorial” disease e.g. cancer
what are the symbols and meanings for a pedigree drawing?
what is the percentage of shared genes within first degree relatives?
- offspring is 50% unless identical twins, then 100% of genetics are shared
what is the percentage of shared genes within second degree relatives (cousins)
25% percentage of shared genes
what is the percentage of shared genes within third degree relatives?
12.5% of genes shared
describe autosomal dominant inheritance
- only 1 faulty copy of gene to cause disease
-if the mutation on the allele is autosomal dominant, then the disease is seen in all generations
- there is a 50% risk of offspring being affected if a parent is affected
- the disease severity can be variable, as some individuals with a mutation may not show disease
- male and females are equally likely to be affected
- example: Marfan’s syndrome, mutations in Fibrillin 1 (FBN1)
describe autosomal recessive inheritance
- 2 faulty copies of a gene is needed to cause disease
- often only one generation affected
- 1 in 4 risk of an affected child if parent’s carriers
-
increased likelihood in consanguineous families (inbred)example: sickle cell anaemia
- single cell base pair change within the coding sequence of the relevant gene and changes one amino acid that produces the disease if you inherit 2 mutated version
GAG=glutamate
GTG=valine
