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Flashcards in Final Exam Deck (66)
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1
Q

What are the 5 points of control?

A
  1. CHROMATIN stage - Histone (compact DNA) methylation and acetylation.
  2. Transcriptional stage - Promoters, exon shuffling.
  3. Translational stage/RNA transport.
  4. Post translational control into cytoplasm.
  5. Post translational modification - folding, cutting, phosphorylation.
2
Q

**Why is it called fragile X syndrome, what determines its severity, what’s the cause?

A

*MC inherited form of mental retardation.

Expansion from pre- to full mutation only occurs through female meiosis.

Severity of dz correlates w/ # of CGG repeats.

caused by the expansion or lengthening of the FMR1 gene on the X chromosome, known as a gene mutation

3
Q

**What are the characteristics and karyotype numbers of Turner’s syndrome?

A

45X, 46XX, 47XXX.

Only monosomy that is consistent with life because it’s not autosomal.

  • Short stature
  • Ovarian dysgenesis
  • Neurocognitive problems
4
Q

**What are the characteristics and karyotype numbers of Klinefelter’s syndrome?

A

47XXY (heraphrodite)

  • Presence of both sex organs is rare.
  • Hypogonadism
  • Weaker muscles as kids.
  • Tall teens, weaker bones, larger breasts, less hair.
  • Adults look similar to males, still taller.
5
Q

**What are the characteristics and karyotype numbers of XYY?

A

47XYY

  • Aliens 3 syndrome.
  • Taller stature.
6
Q

**What are proto-oncogenes? Where in the cell do proto-oncogenes become oncogenes?

A

A proto-oncogene is a normal gene coding for proteins that regulate cell growth and differentiation. They could become an oncogene due to mutations or increased expression in the following:

  • Receptors
  • Messenger systems
  • Nuclear transcription
7
Q

What happens when HER2/neu (ERB2) becomes amplified?

A

Breast cancer

8
Q

What happens when RET has a point mutation?

A

MEN 2 a and b

9
Q

What two things can go wrong with cellular messaging systems?

A

Point mutations and translocation

10
Q

What happens when there is a point mutation on RAS?

A
  • Colon cancer
  • Pancreatic cancer
  • Leukemia
11
Q

What happens when there translocation on ABL?

A

CML

12
Q

What happens with a translocation on c-MYC?

A

Burkitt’s lymphoma

13
Q

What happens with amplification of n-MYC?

A

Neuroblastoma

14
Q

Are oncogenes gain or loss of function? Do they require one or both alleles?

A

Gain of function.

Need only one allele (one hit process)

15
Q

**Are tumor suppressors gain or loss of function? Do they require one or both alleles?

A

Loss of function

Need both alleles (two hit process)

16
Q

Are tumor markers used to diagnose cancer?

A

No, they are used for follow up

17
Q

What are tumor markers useful for? (5)

A
  • Screening
  • Prognosis
  • Determining Tx
  • Evaluating Tx
  • Monitoring recurrence
18
Q

**What is gene linkage?

A

Genes are considered linked when there occur very close to one another on the same chromosome. Mechanically, this means that there are unlikely to cross over.

gene linkage is the tendency of DNA sequences that are close together on a chromosome to be inherited together during the meiosis phase of sexual reproduction.

19
Q

Which polymorphism occurs in Huntington disease and Fragile X?

A
  • Huntington = CAG repeat

- Fragile X = CGG repeat

20
Q

**Why are VNTRs valuable to us?

A

DNA polymorphism used for

  • paternity testing
  • forensics

VNTR loci are very similar between closely related humans, but so variable that unrelated individuals are extremely unlikely to have the same VNTRs

21
Q

**What are the fetal loss rates with amniocentesis and CVS?

A
Amnio = 0.5%
CVS = 1%
22
Q

How soon can you do CVS?

A

10-12 weeks gestation.

23
Q

How soon can you do amnio?

A

16 weeks gestation.

24
Q

When testing for inborn errors of metabolism, when is the preferred time to collect the sample?

A

When the child is the sickest.

25
Q

What is XLID? What is its significance?

A
  • X-linked intellectual disability

- “things go to hell really fast/lots of mental d/o”

26
Q

When can cfDNA be taken from mother’s blood?

A

9 weeks.

27
Q

How does cfDNA work?

A
  • used to screen for abnormalities.
    The idea is 3-13% of all maternal cfDNA is actually from the placenta so you can get a sense of what’s going on with the fetus.

Not very sensitive.

28
Q

What is the normal function of BRCA 1?

A

Caretaker gene that repairs DNA. It repairs DNA when both strands are broken.

29
Q

What happens when BRCA 1 mutates?

A

Breast cancer risk? Same for BRCA 2?

30
Q

What is the normal function of BRCA 2?

A

Binds single strand DNA and directly interacts w/ recombinase RAD51 to stimulate strand invasion and recombination.

31
Q

What happens when men have a BRCA 1 mutation?

A

Male BRCA 1 mutation carriers have a cumulative breast CA risk of 1.2% by age 70; also increase risk of prostate CA.

32
Q

What happens when men have a BRCA 2 mutation?

A

Male BRCA 2 mutation carriers have up to a 15% prostate CA risk, & a cumulative breast CA risk of 6.8% by ages 65 & 70, respectively.

33
Q

What is the function of RAD51?

A

BRCA1, BRCA 2, & RAD-51 influence DNA damage repair & play a role in maintaining the stability of the human genome.

34
Q

What is the founder effect?

A

Founder effect= certain mutation is common to a well-defined population group and can, in theory, be traced back to a common ancestor.

35
Q

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

A

Iceland, single BRCA2 mutation

36
Q

**What happens in the very rare case where you get a person where both BRCA2 alleles are mutated (homozygous)?

A

Fanconi anemia

37
Q

Do we know what happens if a person is homozygous for BRCA 1 mutations?

A

Not really, as such families have not been systematically studied.

38
Q

What types of DNA breaks does the BRCA1 repair? BRCA2?

A
  • BRCA 1= double stranded

- BRCA 2= single stranded

39
Q

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

A

Multisite 3-point BRCA analysis.

40
Q

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

A

Single site BRCA test.

41
Q

**What does the Hardy-Weinberg Principle contend? Why do we care, clinically?

A
  • How variation is maintained in a Mendelian population.
  • Frequencies of alleles will remain constant in the absence of selection, mutation, migration and genetic drift.

Clinically?

  • Constant and predictable relationship between genotype and allele frequency
  • Equilibrium refers to this stability of allele frequencies over time
  • e.g. Wanting to know chances of marrying a carrier of a certain disease
  • (p2, q2 equation)
42
Q

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

A

Condition that affects many parts of the body → hemihyperplasia.
Associated with IVF

43
Q

How has CMA testing increased the yield in genetic testing?

A
  • More detailed than karyotype.
  • Systematically moves down the chromosome and measures how much DNA is there.
  • Better than FISH & G-band karyotyping in the evaluation of patients w/ developmental delay and mental retardation.
44
Q

How does the MTHFR 667 mutation work?

A

It produces a MTHFR variant that has reduced activity at higher temperatures, leading to increased homocysteine in the blood.

45
Q

How does the MTHFR 1298 mutation work?

A

Heterozygus - 20% loss.

Homozygus - 40% loss.

46
Q

What are the NCCN guidelines for people who are at increased risk of breast cancer but don’t have a BRCA mutation?

A
  • Breast self-exam training at age 18.
  • CBE q6-12 months at age 25.
  • Annual mammography and breast MRI screening at age 30-35.
47
Q

What are the NCCN guidelines for people who are at increased risk of ovarian cancer but don’t have a BRCA mutation?

A
  • Consider risk reducing oophorectomy, after childbearing.

- Consider TVUS & CA-125 analysis q 6 months beginning at 35 years of age.

48
Q

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

A

It looks for very small deletions (<1MB) that cause idiopathic mental retardation.

49
Q

What is the significance of the Chromosome Instability Pathway as it relates to colon cancer?

A

It is one of the molecular pathways that benign adenomatous polyps follow in their progression from benign polyp → malignant CA.

50
Q

What is the significance of the “Serrated Adenoma Pathway”?

A

It is one of the molecular pathways that benign adenomatous polyps follow in their progression from benign polyp → malignant CA.

Serrated adenomas are a variant of hyperplastic polyps.

Usually occur in R colon of middle aged F, & have increased risk of malignant transformation.

51
Q

What are the common indications for genetic testing?

A
  • *fetus w/ 1 or multiple anomalies
  • newborns w/ anomalies or dysmorphic features
  • child growth deficiency
  • developmental delay
  • autism
  • delayed pubertal development
  • *fhx of childhood onset d/o (pediatric tumors, etc.)
52
Q

How is Global Developmental Delay (GDD) distinguished from other disorders causing intellectual delay?

A

It doesn’t worsen over time (doesn’t improve either.

Many will not present with syndromic features or a FHx.

53
Q

Which cancer does tumor marker AFP correspond to?

A

Liver Cancer

54
Q

Which cancer does tumor marker CA19-9 correspond to?

A

Pancreatic Cancer

55
Q

Which cancer does tumor marker CA125 correspond to?

A

Ovarian Cancer

56
Q

Which cancer does tumor marker Beta-HCG correspond to?

A

Testicular Cancer

57
Q

Which cancer does tumor marker PSA correspond to?

A

Prostate Cancer

58
Q

Which cancer does tumor marker BRCA1/2 correspond to?

A

Breast Cancer

59
Q

Which cancer does tumor marker CEA correspond to?

A

Colon Cancer

60
Q

Describe the relationship between Crossover, Recombination And Linkage

A

Genes, are said to be linked when they occur in close proximity to one another on the same chromosome
During meiosis recombination occurs multiple times at random locations through a process known as crossover
If two genes are very close to each other on the chromosome -then they are tightly linked -and will be unlikely to crossover for mechanical reasons
Recombination frequency provides a means of assessing the distance between loci on chromosomes

61
Q

What are the primary differences between single gene disorders and common diseases?

A

Single Gene Disorder: A variant in a single gene is the primary determinant of this disease. It is responsible for most of the disease risk with possible minor contribution from the modifier genes or environment. Common Disease: Complex–With many variants of small effects contributing to the disease risk, along with environmental factors, causation is complex-but can have substantial genetic components, as they tend to cluster in families but do not conform to Mendelian pedigree patterns.

62
Q

How is recurrence risk calculated for common diseases?

A

empirically (based on direct observation of data, cohort studies) because the genes and environmental factors of multifactorial traits have not been specifically identified.

63
Q

Monozygotic twins are…

A

“identical”, meaning that they develop from one zygote that splits and forms two embryos

64
Q

dizygotic twins are…

A

“fraternal”, they develop from two separate eggs that are fertilized by two separate sperm.

65
Q

What does p53 do, and what happens if it is mutated?

A

p53 is a gene and a protein that stops cells with damaged DNA from entering the S phase and replicating its DNA thus keeping mutation rate and cancer risk low. If it is mutated, people have increased risk (higher liability) for several cancers

66
Q

What is genetic liability? How does it relate to common diseases?

A

It is basically risk. If people with the p53 heterozygous mutation take a “2nd hit” like a somatic loss of function mutation during their lifetime, this leads to cancer.