Genetics

Question 1

Penetrance

Answer 1

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

Question 2

incomplete (reduced) penetrance

Answer 2

clinical sx present in some individuals with a mutation

Question 3

complete penetrance

Answer 3

clinical sx present in all individuals with a mutation

Question 4

Consanguinity

Answer 4

genetic relatedness between individuals descended from at least one common ancestor

Question 5

Anticipation

Answer 5

the tendency in certain genetic disorders for individuals in successive generations to present at an earlier age and/or with more severe manifestations

Question 6

Common cause of anticipation

Answer 6

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

Question 7

Somatic vs. germline mosaicism

Answer 7

Germline: mutation confined to germ cells and can be transmitted to offspring

Somatic: cannot be transmitted to offspring unless present in germline

Question 8

Balanced chromosome inversion

Answer 8

no net loss/gain of genetic material

Usually no phenotypic abnormalities

Question 9

Unbalanced chromosome inversion

Answer 9

nearly always have phenotypic chx

Question 10

X-linked dominant phenotype expression

Answer 10

phenotype expressed by heterozygous females and hemizygous males

Question 11

X-linked recessive phenotype expression

Answer 11

phenotype expressed by homozygous females and hemizygous males

Question 12

Mitochondrial inheritance

Answer 12

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

Question 13

Genomic imprinting

Answer 13

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

Question 14

Uniparental disomy (UPD)

Answer 14

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

Question 15

Predictive testing

Answer 15

offered to asymptomatic individuals with a family history of a genetic disorder and a potential risk of eventually developing the disorder

Question 16

Presymptomatic predictive testing

Answer 16

certain development of findings related to a specific diagnosis at some future point

Mutation causes disease

Negative result excludes the diagnosis

Question 17

Prdispositional predictive testing

Answer 17

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

Question 18

Duchenne muscular dystrophy genetics

Answer 18

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

Question 19

Hereditary hemochromatosis (HHC) genetics

Answer 19

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

Question 20

Cystic fibrosis genetics

Answer 20

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

Question 21

Hereditary breast and ovarian cancer (HBOC)

Answer 21

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

Question 22

Familial adenomatous polyposis (FAP)

Answer 22

Colorectal cancer

Inactivation of tumor suppressor gene, APC, on chromosome 5

Fairly rare autosomal dominant condition

Question 23

Hereditary nonpolyposis colorectal cancer (HNPCC)

Answer 23

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