Lecture 8 Flashcards
What are spontaneous mutations?
Mutations from naturally occurring errors in DNA replication
What are the two types of mutations?
Spontaneous and induced
What are induced mutations?
Mutations caused by exposure to mutagens
What is a de novo germline mutation?
A new mutation that occurs (spontaneously or induced) in the egg or sperm in an individual who didn’t inherit that mutation
What is copy number variation (CNV)?
Insertion/deletion of chromosome fragments
What does copy number variation result in?
A different number of copies of a particular gene between individuals
CNV amplification of what gene causes increased breast cancer progression?
HER2
HER2 overexpression is found in what percent of breast cancer patients?
Over 30%
Splice-site mutations can cause _____
Deletion of exons or inclusion of introns
Neurofibromatosis type 1 is cause by what mutation?
Splice site mutation that mutates the neural tumor suppressor gene NF1
What type of gene is NF1?
Autosomal dominant, completely penetrant
What does neurofibromatosis type 1 cause?
Neurofibromas – tumors of the nervous system
What splice site exon deletion may cause breast cancer?
Exon deletion in gene for the androgen receptor (AR)
What are the two types of point mutations?
Transition and transversion
What is a transition mutation?
When a pyrimidine is changed to a different pyrimidine, or a purine is changed to a different purine
What is a transversion mutation?
When a purine is changed to a pyrimidine, or a pyrimidine is changed to a purine
Where can sporadic cancer mutations be detected by genomic DNA analysis?
ONLY in tumor cells, not in the other cells of the body
Is sporadic cancer somatic or germline?
Somatic
What causes familial cancer?
Mixture of environmental factors and genetics
The majority of inheritable cancers exhibit what mode of inheritance?
Autosomal dominant
How many copies of a mutated allele are required for the expression of an autosomal dominant trait?
Only one copy of the allele
Li-Fraumeni Syndrome is an example of what kind of inheritable cancer?
Autosomal dominant
What gene is mutated in Li-Fraumni Syndrome?
p53
What does Li-Fraumeni Syndrome cause?
Increased incidence of a broad spectrum of cancers
p53 Gain of Function mutations causes what?
Abnormal aggregation of the protein, which disrupts protein function and leads to autosomal dominant cancer
What is Familial Adenomatous Polyposis (FAP)?
Autosomal dominant cancer that’s causes mutations of the APC tumor suppressor gene
Children with an autosomal recessive condition typically have/don’t have affected parents?
Don’t have
What form of inheritance skips generations?
Autosomal recessive
What is ataxia-telangiectasia?
Autosomal recessive cancer caused by mutation of the ATM gene
What are the symptoms of ataxia-telangiectasia?
Poor coordination and movement due to neurodegeneration; permanent dilated capillaries in the skin and eyes
What is the ATM gene?
Master kinase regulators of checkpoint pathways that recognizes DNA damage
What is Bloom Syndrome?
Autosomal recessive disease that causes small statue, sun sensitivity, male infertility, and a predisposition to a variety of early onset cancers
What gene is mutated in Bloom Syndrome?
BLM
What does the gene BLM code for?
A member of the RecQ family of DNA helicases
What are the three types of x-y linked inheritance?
X-linked recessive, X-linked dominant, and Y-linked
What is Incontinentia Pigmenti?
X-linked dominant disorder that predisposes individuals to skin lesions and cancers of the kidney
What gene is mutated in Incontentia Pigmenti?
NEMO/IKBKG gene
What is Dyskeratosis congenita?
X-linked recessive disorder that resembles premature aging
What genes are mutated in DKC?
The telomerase genes DKC1, TERC, TERT, TINF2
What is RBMY?
RNA-binding motif gene on Y chromosome
Where is RBMY activated as an oncogene?
Make liver cancers
What affects penetrance?
Age, modifier genes, environment
What is mosaicism?
Two of more genetically distinct populations of cells in one individual
What is linkage analysis?
Attempt to locate disease-causing gene by identifying traits that are co-inherited with it
What is the measure of deviation from random association for a pair of alleles?
Linkage disequilibrium (LD)
High LD is indicative of?
No recombination
Low LD is indicative of?
Recombination
What are four options you have if you’re at risk for familial cancer?
Prevention, increased surveillance, risk-reducing surgery, medical intervention
