Q2-FUN13/Human Genetic Variability and its Consequences Flashcards
What are the two main types of germline genetic variation?
large scale and small scale
what are the 3 main types of large scale germ-line genetic variation?
aneupolidy, translocations/inversion, copy number variants
What is aneuploidy?
it is when 1+ individual chromosmes are present in an extra copy or are missing
what is a common example of aneuploidy?
trisomy of chromosome 21 (down syndrome)
what is the incidence of aneuploidy?
rare (approx 1:1000 newborns)
what is the clinical relevance/consequence of aneuploidy?
Usually causes large-scale changes in gene expression with associated clinical consequences (e.g. learning disability, development delay)
What are some other less common viable trisomys?
chromosome 13 (patau syndrome)
chromosome 18 (edwards syndrome)
XXY (Kleinefelters)
What is a type of viable monosomy?
X - Turner female
What is a translocation/inversion?
it is the exchange of DNA during meiosis between 2 different chromosomes
what is the incidence of translocatoins/inversions?
approx 1:500 newborns
what is the clinical relevance/consequence of translocations/inversions?
there could be a net gain or loss of DNA or a disruption of gene sequence
do translocations/inversions have an effect on meiosis?
yes they do
What is a large scale copy number variant?
they are deletions or dupllications of DNA of over 1000 base pairs in size. (can go up to many millions)
What is the incidence of copy number varients?
we all carry multiple copy number variants in our genome
What is the clinical relevance/consequence of copy number variants?
most are benign, but larger ones (over 1M bp) can be pathogenic
the ones over 1M bp cause learning diabilities, autism, epilepsy, etc.
what are microsatellites?
they are short (2-5 bp) repeat units in a DNA sequence
Where are microsatellites usually found?
most are in the noncoding region
What is the incidence of microsatellites?
they are common, we all carry approx 10K microsatellites in our genomes
What is the clinical relevance of microsatellites?
they rarely cause diesease, most are benign
What is a single nucleotide polymorphism?
it is a single bp change in the DNA. commonly referred to as SNPs
What is the incidence of SNP’s?
we all have abt 3.5M SNPs
What is the clinical relevance/consequence of SNPs?
most are benign or have a very small effect on disease, but in rare cases they can be strong/disease causing
What is an insertion and deletion?
it is a small section of DNA (1-few) that are deleted or added in
What is the incidence of insertions or deletions?
we all have approx 20K in our genomes
What is the clinical relevance of insertions and deletions?
rarely cause diesease and most are benign, can be damaging if in exons
Explain pathogenic mutations?
most mutations are outside of genes (only 2% of the genome is “genic”). so most mutations dont cause disease
What are some things pathogenic mutations can do? (5)
What can large scale pathogenic variation result in?
significant change in gene expression because proteins levels from different genes can be changed
What can small scale pathogenic variation result in?
- Changing of amino-acid sequence (one or more amino acids different)
– Skipping or introduction of an exon (aberrant splicing)
– Premature stop to translation
what are the different classes of genetic mutations?
Is cancer considered somatic or germ-line?
somatic
the accumulation of somatic mutations can lead to _______.
cancer
explain why cancer is not a single disease.
- different cancers come from different tissues
- in a cancer, there can be different types of cancer cells
- some cancer cells can be sensitive to one cure but not another cure
- genetic characterization of cancer is a growing field
