Genetics Flashcards
Exam II
Penetrance
the proportion of individuals with a mutation causing a particular disorder who exhibit clinical symptoms of that disorder
(# individuals with clinical features / # individuals with a disease causing mutation) x 100
incomplete (reduced) penetrance
clinical sx present in some individuals with a mutation
complete penetrance
clinical sx present in all individuals with a mutation
Consanguinity
genetic relatedness between individuals descended from at least one common ancestor
Anticipation
the tendency in certain genetic disorders for individuals in successive generations to present at an earlier age and/or with more severe manifestations
Common cause of anticipation
Often observed in disorders resulting from the expression of a trinucleotide repeat mutation that tends to increase in size and have a more significant effect when passed from one generation to the next
Somatic vs. germline mosaicism
Germline: mutation confined to germ cells and can be transmitted to offspring
Somatic: cannot be transmitted to offspring unless present in germline
Balanced chromosome inversion
no net loss/gain of genetic material
Usually no phenotypic abnormalities
Unbalanced chromosome inversion
nearly always have phenotypic chx
X-linked dominant phenotype expression
phenotype expressed by heterozygous females and hemizygous males
X-linked recessive phenotype expression
phenotype expressed by homozygous females and hemizygous males
Mitochondrial inheritance
Mitochondria contain their own distinct genome, and mutations in mitochondrial genes are responsible for several recognized syndromes
Always maternally inherited, since ova contain mitochondria, and sperm do not
Genomic imprinting
The epigenetic phenomenon by which certain genes are expressed in a parent-of-origin-specific manner:
If the allele inherited from the father is imprinted, it is thereby silenced, and only the allele from the mother is expressed
If the allele from the mother is imprinted, then only the allele from the father is expressed
Ex. Paternal inheritance of a deletion in a certain region is associated with Prader-Willi syndrome, whereas maternal inheritance of the same deletion is associated with Angelman syndrome
Uniparental disomy (UPD)
Occurs when a person receives two copies of a chromosome, or of part of a chromosome, from one parent and no copy from the other parent
Most often result in no phenotypical anomalies
Should be suspected if an individual manifests a recessive disorder where only one parent is a carrier
Predictive testing
offered to asymptomatic individuals with a family history of a genetic disorder and a potential risk of eventually developing the disorder
Presymptomatic predictive testing
certain development of findings related to a specific diagnosis at some future point
Mutation causes disease
Negative result excludes the diagnosis
Prdispositional predictive testing
eventual development of findings related to a specific diagnosis is likely but not certain
Mutation confers susceptibility
A negative result may not exclude the possibility of future development of the disease from other causes
Duchenne muscular dystrophy genetics
Deletions or duplications in the DMD gene detected in 65% of cases
DNA analysis of the DMD gene via blood sampling is a less expensive and less invasive primary diagnostic approach than dystrophin analysis via muscle biopsy
Hereditary hemochromatosis (HHC) genetics
When clinical features and/or serum transferrin iron saturation and serum iron concentration are consistent with HHC, molecular genetic testing is less expensive and less invasive than liver biopsy in confirming the diagnosis
Known disease-causing HFE mutations are detected in approximately 87% of cases of HHC
Cystic fibrosis genetics
Using a panel of the most common CFTR mutations, approximately 90% of patients of non-Ashkenazi Jewish Caucasian heritage will have detectable mutations
However, for an individual of any ethnicity, sweat chloride testing is a more accurate diagnostic test
Hereditary breast and ovarian cancer (HBOC)
Associated with mutations in tumor suppressor gene BRCA 1 and BRCA 2 on chromosomes 17 & 13, respectfully
Inherited in autosomal dominant manner
Early age of onset of cancers, multiple breast and/or ovarian cancers across generations, breast cancer in males
Women with family histories of early onset BC/ OC or younger women (<50 yrs) diagnosed with BC/OC can have the BRCA mutation test
Can choose to increase surveillance or to have prophylactic breast and/or ovarian surgery
Can assist in developing a treatment plan in younger women already diagnosed with BC/OC
Familial adenomatous polyposis (FAP)
Colorectal cancer
Inactivation of tumor suppressor gene, APC, on chromosome 5
Fairly rare autosomal dominant condition
Hereditary nonpolyposis colorectal cancer (HNPCC)
4 mismatch repair genes (MSH2, MLH1, MSH6, PMS2) have been identified
More common—represents up to 10% of all CRC’s
Autosomal dominant
In a large prospective study, colonoscopy every 3 years in individuals at risk for HNPCC reduced the risk of developing CRC by 62% and prevented disease-related deaths
