Final Exam Flashcards
What percentage of DS is due to trisomy 21 like in karyotype?
95% of cases involve trisomy 21.
90% involve maternal meiosis, MI
10% involve paternal meiosis, MII
A woman is a carrier of a balanced Robertsonian translocation between chromosomes 14 and 21. On average, how many of her gametes will be viable?
50%
A woman and her brother are carriers of a balanced Robertsoniantranslocation
between chromosomes 14 and 21. Who has the highest risk to have a child
with Down syndrome?
Risk is always higher to a female.
The woman with the translocation has a baby with Down
Syndrome. How many chromosomes does this baby have? How many
copies of chromosome 21?
The baby has 46, with 3 copies of chromosome 21 (third 21 has 14 stuck to it, there is only one 14 by itself - so three 21 and only one 14 in the end still 46 chromosomes)
A man has a child with Prader-Willi syndrome. His sister has a child with Angelman syndrome. How do you explain this?
They are each carriers of a balanced translocation involving chromosome 15. PWS is paternal chromosome 15 70% of the time. AS is maternal chromosome 15 70% of the time
Thinking about Turner syndrome:
- What would the karyotype show?
- How many are spontantously aborted?
1.
45, X
2.
99%
What is unique about Turner syndrome?
How many Barr bodies would you see?
Only viable monosomy in humans.
0 (zero) Barr bodies (b/c only one X chromosome even exists)
Who is phenotypically normal?
- 45, X
- 45, XX, t(14;21)
- 46, XX
- 46, XY
- 46, XX, t(14;21), +21
- 47, XXY
Normal:
- 45, XX, t(14;21)
- 46, XX
- 46, XY
Abnormal:
- 45, X - Turner’s Syndrome
- 46, XX, t(14;21), +21 - Robertsonian Down syndrome
- 47, XXY - Kleinfelter
What is the worst Robertsonian translocation you can imagine? Why?
(21;21)
Fetus will almost always have Down syndrome
unless there is also nondisjunction by other parent
In what disorder does nondisjunction always occur in male meiosis II?
47, XYY (XYY Male)
Why would someone have a karyotype?
Problems of early growth and development (ambiguous genitalia)
Dysmorphic features (something different about how they look)
Stillbirth and neonatal death
Fertility problems, both male and female
Family history of chromosome abnormalities
Neoplasia
Pregnancy in woman of advanced maternal age
When is genetic testing of minors usually ok?
For conditions that can manifest before age 18
It has been reported that type I osteogenesis imperfecta (OI) patients with dentinogenesis imperfecta (DI) are more likely to have fractures at birth than those without DI. What is the underlying molecular mechanism for type I OI with DI? A.Gain of function. B.Haploinsufficiency C.Loss of function D.Dominant negative
D. Dominant negative
You need to figure out where to send a patient sample for genetic testing.
What resource can you use to find an appropriate lab?
Genetic Testing Registry
A couple present for genetic counseling after the birth of their son who has a multifactorial trait for which females are more commonly affected. Regarding recurrence risks, what do you tell them?
a. Their recurrence risk is higher than if a daughter had been affected, and the subsequent risk is higher for a daughter than a son.
b. Their recurrence risk is higher than if a daughter had been affected, and the subsequent risk is higher for a son than a daughter.
c. Their recurrence risk is lower than if a daughter had been affected, and the subsequent risk is higher for a daughter than a son.
d. Their recurrence risk is lower than if a daughter had been affected, and the subsequent risk is higher for a son than a daughter.
e. The recurrence risk is 50%
a.Their recurrence risk is higher than if a daughter had been affected, and the subsequent risk is higher for a daughter than a son.
What is triploidy?
69 chromosomes.
Most common mechanism is fertilization of ovum by 2 sperm.
Babies can be born but don’t live long
What is tetraploidy?
92 chromosomes. Karyotype is 92, XXXX or 92, XXYY (failure of completion of early cleavage division of the zygote). Embryos, no babies. 3x less common than triploidy.
Phenocopy?
Phenotype produced by exposure to environmental agent that
looks like genetic disorder
Polygenic?
Multiple genes contribute to phenotype, usually each with a
small contribution; important in complex traits like diabetes
Multifactorial?
Genes and environment contribute to phenotype
Genes and environment contribute to phenotype
- Number of affected individuals: more = higher risk.
- severity: more severe = higher risk.
- If individual is of sex least affected, recurrent risk is higher.
How is genetic testing different from other types of medical tests?
It has implications for other family members.
What does whole exome sequencing primarily focus on?
Coding regions (exons) of known genes - about 2% of the genome
What bill was passed to try and prevent genetic discrimination in
obtaining a job and health insurance?
Genetic Information Nondiscrimination Act (GINA)
T/F Robertsonian translocations are translocations between two metacentric chromosomes.
F. They are between Acrocentric chromosomes (13, 14, 15, 21, 22)
T/F Balanced translocation carriers are not at risk to have unbalanced offspring.
F (infertility problems are often how translocation carriers are ascertained)
T/F Of the gametes that a carrier of a (14;21) Robertsonian translocation can make, ½ are not viable.
T
T/F In a female with a translocation between an autosome and the X chromosome, the normal X will be preferentially inactivated.
T
All of the following mechanisms are explanations for why a female may be affected with an X-linked recessive disorder (like hemophilia or Duchenne muscular dystrophy) EXCEPT
a. Skewed X inactivation
b. Uniparental disomy from either an affected father or carrier mother
c. Turner syndrome
d. Consanguinity
e. Mutation in the pseudoautosomal region of the Y chromosome
f. Balanced translocation between an autosome and the X chromosome
(Which one is MOST likely?)
e. Mutation in the pseudoautosomal region of the Y chromosome.
(a. Skewed X-inactivation most likely)
PWS and AS are the best examples in humans of __________?
imprinting
Triploid fetuses have ______ chromosomes? (Are there any liveborns? Mechanism?)
69; live births occur but babies die shortly thereafter; fertilization by two sperm most common
Tetraploid fetuses have ______ chromosomes? (Are there any liveborns? Mechanism?)
92; no live births; failure of completion of cleavage in early embryo
Match the mutation with its name:
- p.Gly180Arg a. missense
- p.Gly180* b. frameshift
- p.Gly180Gly c. nonsense
- p.Gly180Serfs*4 d. silent
- a
- c
- d
- b
(p. Gly180Serfs*4 is a frameshift mutation, but you can’t tell from this designation whether or not it is an insertion or deletion.)
Whole exome sequencing can identify mutations in
a. Promoters
b. Exons
c. Introns
d. Mitochondrial DNA
e. A, b and c
Whole exome sequencing mainly detects mutations in coding exons.
A male calico cat is the equivalent of what human disorder?
a. Turner syndrome
b. Klinefelter syndrome
c. 47,XYY
d. 47,XXX
e. Down syndrome
b. Klinefelter syndrome
Different clinical phenotypes caused by mutations in the same gene is
a. Allelic heterogeneity
b. Clinical heterogeneity
c. Locus heterogeneity
d. Variable expressivity
e. None of the above
b. Clinical heterogeneity (Make sure you understand all 4 types of heterogeneity: allelic, clinical, genetic and locus.)
Mitochondrial DNA can be used to link
a. A woman and all of her children and all of her children’s descendents
b. A woman and all of her children and all of her daughter’s descendents
c. A man and all of his children and all of his children’s descendents
d. A man and all of his children and all of his son’s descendents
A woman and all of her children and all of her daughter’s descendents.
(Remember only passed on by mother. You can use Y chromosome polymorphisms to trace males. That was what was used to try and determine whether or not Thomas Jefferson fathered a child by his slave.)
Match the location of the trinucleotide repeat with the disorder
a. Fragile X syndrome 1. 3’ UTR
b. Huntington disease 2. 5’ UTR
c. Myotonic dystrophy 3. Intron
d. Freidreich ataxia 4. Coding region
Fragile X=2 (5’UTR), HD=4 (coding for glutamine), Myotonic=1 (3’UTR), Freidreich ataxia = 3 (intron). Freidreich ataxia is the only autosomal recessive disorder currently known to be due to a trinucleotide repeat expansion.
(Remember if a disorder is associated with thousands of repeats, it does not occur in the coding region. Also if you have hundreds or thousands of repeats, you need to use Southern blot to determine the number of repeats)
Which statement regarding performing genetic testing on minors is correct?
a. No guidelines exist for performing genetic testing on minors.
b. It is appropriate to test minors for whatever tests the parents request.
c. It is appropriate to test minors for adult onset disorders.
d. It is appropriate to test minors for conditions with onset of symptoms before age 18.
d. It is appropriate to test minors for conditions with onset of symptoms before age 18. (Remember that minors are only tested for disorders that manifest in childhood).
Which of the following is NOT an indication for chromosome analysis?
a. Baby with ambiguous genitalia
b. Couple who have had 3 or more miscarriages
c. Child with sickle cell anemia
d. Newborn with a heart defect who has features that suggest trisomy 18
e. A woman whose sister is a balanced translocation carrier
c. Child with sickle cell anemia.
Sickle cell anemia is due to a missense mutation (substitution of one amino acid for another)
For Prader-Willi syndrome (PWS) and Angelman syndromes (AS), match the term with explanation/definition. Some terms may be used more than once.
a. 50% 1. Most common mechanism in both disorders
b. AS 2. Recurrence risk (RR) if UPD is underlying mechanism
c. Deletion 3. RR if inherited methylation defect is mechanism
d. PWS 4. Contiguous gene syndrome
e. Maternal 5. PWS results from absence of _____ contribution
f. Paternal 6. AS results from absence of _____ contribution
g. FISH 7. Can result from mutation in single gene
h.
- c
- h
- a
- d
- f
- e
- b
- j
- h
- g
- d
- b
- i
(So important to determine underlying molecular defect so appropriate recurrence risks can be counseled. Now truly test your knowledge: which one of the seven dwarves had AS? I swear this was an actual presentation at a scientific meeting.)
