Genetics-Genetic Testing

Question 1

6 types of genetic testing

Answer 1

Carrier detection, prenatal diagnosis, newborn screening, presymptomatic diagnosis, forensics, research

Question 2

The ability to correctly identify those who have disease. How do you calculate it?

Answer 2

Sensitivity = TP/(TP + FN)

Question 3

The ability to correctly identify those without disease

Answer 3

Specificity = TN/(FP + TN)

Question 4

Positive predictive value

Answer 4

PPV = TP/(TP +FP)

Question 5

Congenital adrenal hyperplasia (CAH) is an inborn error of steroid biosynthesis that may produce ambiguous genitalia in females and adrenal crises in males and females. The screening test has a sensitivity of 95% and specificity of 99%. The prevalence of CAH is 1/10,000 in Caucasians but rises to 1/400 in the Native Alaskan Yupik. Calculate the positive predictive value of the assay in a population of 500,000 Caucasians and in a population of 10,000 Yupik.

Answer 5

1) How many affected individuals are in the population? 500,000/10,000 = 50. 2) How many affected individuals will be detected? 50 x 0.95 = 47 = True positives. 3) How many unaffected individuals are in the population? 500,000 - 50 J = 499,950, basically 500,000. 4) How many unaffected individuals will test negative? .99 x 500,000. 5) How many unaffected individuals will test positive? 0.01 x 500,000 = 5,000 = false positives. PPV = TP/(TP+FP) = 47/(47+5,000) = 0.009.

Question 6

This type of genetic testing identifies individuals with: familial breast cancer (BRCA), hemochromatosis, Huntington’s, APKD, HNPCC and MEN2. Why is this type of testing useful?

Answer 6

Presymptomatic diagnosis: detection of genes before they cause symptoms. These are useful for prevention, prophylaxis, improvement of supervision and reproductive decisions.

Question 7

This type of genetic testing identifies individuals with: PKU, galactosemia, congenital hypothyroidism and sickle cell disease.

Answer 7

Newborn screening

Question 8

This type of genetic testing may decrease the incidence of individuals with: sickle cell disease, Tay-Sachs disease, thalassemia, cystic fibrosis and PKU.

Answer 8

Carrier screening

Question 9

When would you use invasive prenatal diagnostic procedures?

Answer 9

Advanced maternal age, FH, abnormal maternal serum test or risk of neural tube defect.

Question 10

Why does amniocentesis take 10-12 days to get back?

Answer 10

They have to grow the fetal cells from the amniotic fluid before testing cytogenics or DNA

Question 11

Used for rapid fetal cytogenic analysis but has highest risk of miscarriage

Answer 11

Cordocentesis

Question 12

In what setting might you utilize preimplantation genetic diagnosis?

Answer 12

Before implantation as with in vitro fertilization

Question 13

Ultrasound has a sensitivity of 30-50% for most congenital malformations. Which malformations does it have a better sensitivity for?

Answer 13

Anencephaly (100%) and spina bifida (85-90%)

Question 14

Mom with low AFP levels is at risk for what disease? High levels?

Answer 14

Low = Down syndrome. High = spina bifida.

Question 15

What things are tested in the maternal triple test?

Answer 15

Unconjugated estriol, FbetahCG, MSAFP are all assessed for Down syndrome.

Question 16

What is this a sign of?

Answer 16

Increased nuchal translucency is a sign of Down syndrome.

Question 17

What are tools we can use for cytogenic analysis?

Answer 17

Giemsa staining (ID chromosomes), FISH (probe DNA finds gene on chromosome), chromosome painting, spectral karyotypic (SKY colors can tell you where translocations occur), comparative genomic hybridization (CGH compares tumor and normal chromosomes, seeing if there are imbalances in regions expressed on chromosomes) and microarray (assesses gain of genes, loss of genes or balanced genes compared to reference DNA)