final

Question 1

What causes Fragile X?

Answer 1

• A portion of X chromosome dangles by a thread and leads to the MC form of mental retardation (1/1000 males)- most widespread single gene cause of autism.
• Unstable CGG repeat at Xq27.
• Expansion from pre to full mutation only occurs thru FEMALE meiosis.
• Severity of dz correlates with # of CGG repeats.
• Expansion of CGG affects the FMR1 (Fragile X mental retardation 1) gene on X chromosome—> failure to express a protein required for normal neural development


Question 2

Results from XYY?

Answer 2

• Taller than average men.
• “Aliens 3 Syndrome” Clinical phenotype is normal (other than tall stature). NOT excessively violent. (An error in chromosome separation during anaphase II of meiosis II resulting from a process known as nondisjunction leaves sperm cells with an extra copy of the Y-chromosome). This = XYY which occurs in 1/1000 MALE births.

Question 3

What is Klinefelters?

Answer 3

• 47,XXY: “Hermaphrodite disorder”
• Highly misunderstood, predominantly male phenotype, actual presence of both sex organs is exceedingly rare. Hypogonadism = Low testosterone and LH/FSH (not so much testicular atrophy). Weaker muscles and reduced strength, taller than average later. Less muscle, less facial and body hair, broader hips, larger breasts, weaker bones, lower energy. By adulthood males are similar to XY people, mb taller. Mb infertile.

Question 4

3 places in the cell that proto-oncogenes can become oncogenes?

Answer 4

receptors, messenger systems and nuclear transcription

Question 5

What can go wrong with receptor synthesis?

Answer 5

amplification and point mutation

Question 6

Know the 5 points of control

Answer 6

1) Chromatin: Histone methylation. Target sites of histone methylation are cytidines which exist as CG (CpG. Areas with lots of them are CpG islands) Methylation of CpG down regs transcription. Histone acetylation- add an acetyl group, stop further condensing of DNA- encourages active transcription. Generally, methylation upregs transcription and demethylation inhibits. Methyl, Acetyl and Phosphate groups are ones that modify histones.
2) Transcription- Promoters CCATT and TATA boxes. Are in all protein coding genes. Exon shuffling, enhancers (transcription factors bind to enhancer regions)
3) Translation- RNA transport (exportins). Importins and exportins are regulated by GTPases called Ran
4) Post-translation into cytoplasm- Cap/ tail communication
5) Post-translation modification

Question 7

Trisomy 21

Answer 7

Down syndrome – extra chromosome

40% with congenital heart defects, increased risk of ALL, reduced infertility

Question 8

Trisomy 18 Edward Syndrome

Answer 8

Very poor prognosis, AVSD, PDA, hand and foot malformations, low set ears, micrognathia

Question 9

Trisomy 13 – Patau syndrome

Answer 9

Polydactyly, cleft palate, microphthalmia (small eyes), microcephaly, cardiac and renal defects, very poor prognosis

Question 10

Turner syndrome

Answer 10

45,X - 46, XX-47, XXX
Only monosomy consistent with life (bc it’s autosomal)
50% are 45,X. The rest are mosaics with 46, XX and 47, XXX occurring in different cells. Arising from X-chromosome monosomy, Turners’s syndrome results in marked short stature, ovarian dysgenesis and neurocognitive problems. Significantly greater adult height treated with growth hormone injections

Question 11

What can go wrong with the cells messenger system

Answer 11

point mutation and translocation

Question 12

Translocation of chromosome 9,22 on tumor suppressor gene causes Philadelphia chromosome leads to?

Answer 12

CML

Question 13

Translocation of 15,17 leads to?

Answer 13

AML

Question 14

Translocation of 14,18 leads to?

Answer 14

follicular lymphomas

Question 15

Translocation of 8,14 leads to?

Answer 15

Burkitt’s lymphoma

Question 16

Translocation of 11,14 leads to?

Answer 16

mantle cell lymphoma

Question 17

Contrast and compare oncogenes and tumor suppressors. i.e. which provide gain of function and which loss of function. Which process requires just one allele to be bad and which requires the two hit process?

Answer 17

Oncogenes = gain of function; needs mutation in one copy of allele
Tumor suppression = loss of function; needs mutation in both copies allele

Question 18

Are tumor markers usually used to diagnose cancer? If not what are they used for?

Answer 18

Weuse tumor markerstodetectthe presence of certain types of cancerin the body, and to monitor the progress ofcancertreatment.

Question 19

What is the difference between Northern Blot, Southern, Western and Dot Blots?

Answer 19

• Southern blot: analyzes DNA fragments on a gel electrophoresis using a probe
• Northern blot: analyzes RNA fragments on a gel electrophoresis using a probe
• Western blot analyzes proteins on gel electrophoresis using enzyme linked antibody
• Dot blot is used in medical genetics to analyze RNA, DNA, or proteins and DOES NOT use electrophoresis

Question 20

What is gene linkage? How is it used for mapping?

Answer 20

• Linkage maps: distance is measured in the frequency of recombination of coupling arrangements of alleles on linked genes
  - If the gene of interest and the marker are on different chromosomes, the alleles will remain together in an egg or sperm only about 50% of the time and thus are unlinked.
  - If the gene and marker are on the same chromosome but are far apart, the allesles will remain together about 50% of the time, and are also said to be unlinked.
  - If the gene and marker are close together on the same chromosome, a crossover between the two alleles is much less likely to occur and show less than 50% recombination and thus are said to be linked.

Question 21

What types of DNA polymorphisms are there? Which type is used for paternity testing and forensics?

Answer 21

• RFLP) The presence or absence of a restriction site produces DNA fragments of varying lengths, reflecting sequence variation
• VNTR) variation in fragment lengths is produced by differences in number of tandem repeats located between 2 restriction sites. ***Used for paternity testing and forensics
• STRP) variation in fragment lengths is produced by differences in the number of microsatellite repeats found between 2 PCR primer sites
• SNP) are single differences in a nucleotide sequence

Question 22

Which polymorphism occurs in Huntington disease and Fragile X?

Answer 22

VNTR

Question 23

What is the difference in fetal loss rates between amniocentesis and CVS? How soon in pregnancy can each procedure be done?

Answer 23

• Amniocentesis at 16 weeks, risk of fetal demise is 0.5%

- Chorionic Villus sampling (CVS) done at 10-12 weeks, fetal mortality rate is 1%

Question 24

When can cfDNA be taken from the mothers blood, and how does cfDNA work

Answer 24

9 weeks, it’s a blood test that separates fetal DNA from maternal DNA

Question 25

What is the function of BRCA1 and BRCA2? What happens if it becomes mutated? Do men get cancer from these mutations? If so what types?

Answer 25

- BRCA1: caretaker gene, produces breast cancer type 1 susceptibility protein, responsible for repairing damaged DNA or destroying it if not repairable, expressed in mammillary cells and other tissues. If mutated -> various cancers - BRCA2: fx similar to BRCA1 but the mutated protein is much different, binds single strand DNA (BRAC1 – double strand) an ddirectly interacts with the recombinase RAD51 to stimulate strand invasion and recombination * *Breast and ovarian cancer are risks of defective BRCA genes * * males with defective BRCA are at risk for breast CA, melanoma, GB, bile duct, pancreatic and stomach CA, males with BRCA2 -> risk of prostate CA

Question 26

What is the function of RAD51?

Answer 26

In the nucleus of many types of normal cells the BRCA1 protein interacts with RAD51 during repair of DNA double strand breaks. BRCA2 binds single strand DNA and directly interacts with the recombinase RAD51 to stimulate strand invasion and recombination

Question 27

What is the founder effect? In which country is virtually all breast- ovarian cancer (HBOC) a result of just 1 person?

Answer 27

All germ-line BRCA1,2 mutations have been inherited, suggesting a large “founder” effect in which a certain mutation is common to a well-defined population group and can, in theory, be traced back to a common ancestor. Ashkenazi Jews

Question 28

What types of DNA breaks does the BRCA1 repair?

Answer 28

Double strand

Question 29

What types of DNA breaks does the BRCA2 repair?

Answer 29

Single strand

Question 30

Which test is ordered if the person is of Ashkenazi Jewish decent?

Answer 30

a multisite 3 point BRCA analysis

Question 31

If a person has a relative where the gene mutation is already known, what test is ordered?

Answer 31

a single site BRCA test

Question 32

What does the Hardy-Weinberg Principle contend?

Answer 32

Provides a solution to how variation is maintained in a Mendelian population. It contends that the frequencies of alleles will remain constant in the absence of selection, mutation, migration and genetic drift.

Question 33

What is Beckwith–Wiedemann Syndrome and what is its significance?

Answer 33

Overgrowth disorder that is usually present at birth, characterized by an increased risk of childhood cancer and certain congenital features such as abdominal wall defects as hernia, large tongues, and large bodies and or limbs, large adrenal glands, diastasis recti, ear crease or ear pits and neonatal hypoglycemia

Question 34

List some good and bad points to DTC direct to consumer genetic testing

Answer 34

good: potentially lifesaving information bad: inconsistent, false positives/negatives, may not be scientifically validated, result interpretation not always easy, information may be incomplete, anxiety provoking, next steps unclear, not covered by insurance, expensive, not covered by HIPAA

Question 35

How has CMA testing increased the yield in genetic testing?

Answer 35

Microarray-based CGH to detect changes in genomic copy number, more than any other single test, has dramatically increased rate of diagnosis among individuals with unexplained developmental delay and mental retardation

Question 36

How do the genetics of MTHFR work? (i.e. 667 &1298 mutations)

Answer 36

MTHFRR is a key regulatory enzyme in folate and homocysteine metabolism. Disruption of homocysteine influences risk of several complex disorders

Question 37

Know the NCCN guidelines for people why are at increased risk of breast or ovarian cancer, but do not have the well-known BRCA1 or 2 mutations

Answer 37

consider comprehensive BRCA1/BRCA2 testing of patient or if unaffected, test family member with highest likelihood of mutation OR consider multi-gene testing, if appropriate.

Question 38

What are the common indications for genetic testing?

Answer 38

Family history, personal hx of ovarian carcinoma or male breast CA, personal hx prostate CA, pancreatic CA

Question 39

What type of abnormality is the CMA test looking for in terms of mutations

Answer 39

looks for very small deletions (<1MB)

Question 40

How is GDD distinguished from other disorders causing intellectual delay?

Answer 40

CGH broad genomic coverage, with chromosomal microarray

Question 41

What is XLID? What is its significance?

Answer 41

X-linked genetic testing X-linked intellectual disability (XLID) is estimated to account for approx. 10% of all cases of intellectual delay (ID). More than 70 genes responsible for XLID in which mutations have been identified have been cloned. There are more than 100 genes that have been identified by linkage and not yet cloned.