Genetics III - Final Flashcards
Down’s Syndrome is Trisomy____.
21
_____% Down’s Syndrome involves Trisomy 21
95%
Of the 95% of Down’s Syndrome that involve Trisomy 21, ____ % involve ______,____
and _____% involve ______,_____
90% maternal meiosis, MI
10% paternal meiosis, MII
What rearrangement occurs in the Acrocentric Chromosomes?
Robertsonian Translocation
What are the 5 Acrocentric chromosomes?
13, 14, 15, 21, 22
Robertsonian translocations involve ______ hooked together.
Acrocentrics
T/F
Balanced Robersonian translocations involve the long arms of 2 acrocentric chromosomes.
(13,14,15,21,22)
True
A balanced Robertsonian translocation between chromos 14 and 21 will yield how many total chromosomes?
45
If a woman is carrying a balanced Robertsonian translocation between chromos 14 and 21, how many of her gametes will be viable?
50%
A woman and her brother are carriers of a balanced Robertsonian translocation (14 and 21) - which has the highest risk to have a child with Down’s Syndrome?
Female
***always higher with female
A woman with a balanced Robertsonian translocation between 14 and 21 has a Down’s baby - how many chromosomes does the baby have?
How many copies of 21?
46 (NOT 47)
3 copies 21
Most Down’s Syndrome pts have ____ chromosomes
If mother has a translocation of 14 and 21, the Down’s person will have ____ chromosomes
47
46
What could explain a man having a baby with Prader-Willi and his sister having a child with Angleman?
Balanced Translocation involving chromo 15
What is the Karyotype of Turner syndrome?
45, X
How many 45, X (Turner’s) are spontaneously aborted?
99%
What is the only viable monosomy in humans?
only viable hemizygous condition
Turner Syndrome
How many Barr bodies would you see in Turner’s Syndrome?
0
T/F
A Barr body is an inactivated X chromosome in a female and enables Lyonization
True
45, X:
Turner’s
45, XX t(14;21)
phenotypically normal
46, XX
46, XY
normal
46, XX, t(14,21), +21
Down’s
47, XXY
Klinefelters
What is the worst Robinsonian translocation?
21 for 21
fusion of chromosome 21
Where does the nondisjunction that creates 47 XYY occur?
**NOT Klinefelters (47 XXY)
Male Meiosis II
Nondisjuction in Male Meiosis I will result in:
Nondisjuction in Male Meiosis II will result in:
**sex chromosomes
Kleinfelters (XXY)
XYY (or XXX)
7 reasons to have a Karyotype?
Ambiguous genitalia (growth, development)
Dysmorphic features
Stillbirth/neonatal death
Fertility problems
Family history
Neoplasia
Pregnancy in advanced maternal age
When is genetic testing for minors usually ok?
Conditions manifesting before 18
Mechanism of Type I Osteogenesis Imperfecta W/O Dentinogenesis imperfecta:
Haploinsufficiency
Mechanism of Type I Osteogenesis Imperfecta With Dentinogenesis Imperfecta:
Dominant Negative
T/F
Type I Osteogenesis Imperfecta With DI (as opposed to without DI) are more likely to have fractures at birth
True
What resource is to be used for a patient that needs genetic testing?
Genetic Testing Registry
A son has a trait more commonly affecting females - what is the recurrence risk?
(2 things)
More than if female was affected
Greater if you have a daughter
How many chromosomes in Triploidy?
69
What is the most common mechanism that produces Triploidy (69 chromos)?
2 sperm fertilize ovum
What is the Prognosis for Triploidy (60 chromos)?
Babies born but don’t live long
How many chromosomes in Tetraploidy?
92
What is the Karyotype in tetraploidy?
92, XXXX
or
92, XXYY
What is the usual mechanism that creates Tetraploidy?
Failure early division/cleavage in zygote
What is the Prognosis for Tetraploidy (92 chromos)?
Embryos can form - no babies viable
How does Tetraploidy compare to Triploidy?
incidence
3x Less common
How does Triploidy compare to Tetraploidy in terms of incidence?
3x More common
A phenotype produced by exposure to an environmental agent…
(this can look like a genetic disorder)
Phenocopy
When multiple genes contribute to a phenotype…
diabetes
Polygenic
***each has small contribution
When both Genes and the Environment can contribute to a phenotype…
Multifactorial
What are 3 factors that contribute to the recurrence risk of a multifactorial trait like clefting?
Number affected individuals in Family
Severity
If individual is of sex Least affected, recurrent risk higher
What is the one major way genetic testing is different from other types of tests?
Implications for Family Members
Whole Exome sequencing focuses on…
Exons
What bill prevents genetic discrimination?
*in terms of job attainment and Health insurance
GINA
Genetic Info Nondiscrimination Act
T/F
Robertsonian translocations are between metacentric chromos
False
*acrocentric
T/F
Balanced translocation carriers are at risk to have unbalanced offspring
True
*often how identified
T/F
A 14,21 Robertsonian translocation will have 1/2 unviable gametes
True
T/F
The normal X will be turn on in a woman with translocation between autosome and X chromosome.
False
***apparently bad chromo will take over
What is the most likely way a female expressed X-linked recessive disorder?
What is the least likely?
Skewed X inactivation
Mutation pseudoautosomal region Y (females don’t have Y)
T/F
Skewed X expression, Uniparental disomy, Turner’s, Consanguinity, and Balanced translocation from Autosome to X can all uncover X-linked recessive in Females
True
Most common mechanism in PWS and AS?
Deletion
RR if UPD is mechanism of PWS or AS?
less than 1/1000
RR if inherited methylation defect is mechanism for PWS or AS?
50%
Prader-Wili Syndrome, which results from either father’s 15 deletion or Uniparental Disomy from mother, is also…
Contiguous gene syndrome
PWS results from absence of ____ contribution of chromo 15.
AS results from absence of _____ contribution of chromo 15.
Father’s
Mother’s
Angelman Syndrome can result from a mutation is _______.
Single gene
What test provides the highest detection rate for PWS and AS?
What test detects deletions?
Methylation
FISH
If deletion is the mechanism for PWS or AS, what is the recurrence risk?
less than 1/1000
Compulsive eating and developmental delay are seen in what Syndrome?
Prader-Willi
Seizures, Ataxia, and an inability to talk are seen in what Syndrome?
Angelman
If PWS and AS are seen in the same family, what is the most likely mechanism?
Translocation
T/F
PWS and AS are the best examples of Imprinting in humans
True
Triploid have how many chromosomes?
Any viable?
Mechanism?
69
Die as newborn
2 sperm, 1 ovum
Tetraploid fetuses have how many chromosomes?
Viability?
Mechanism?
92
No live births
Early cleavage failure
p. Gly180Arg:
p. Gly180*
p. Gly180Gly
p. Gly180Serfs*4
Missense
Nonsense
Silent
Frameshift
T/F
Whole exome sequencing detects mutations in coding exons
True
Human disorder = Male Calico Cat
Klinefelter’s
Different Clinical phenotypes caused by mutations in the Same Gene is…
Clinical Heterogenicity
T/F
Mito DNA links a woman to all her children and her daughter’s descendants
True
Fragile X:
Huntington’s:
Freidreich ataxia:
Myotonic dystrophy
5’ UTR
1st Exon
Intron
3’ UTR
What is the only Autosomal Recessive disorder currently known to be caused by a Trinucleotide repeat?
Freidreich Ataxia
If a disorder has 1000’s of repeats it does not occur in the _______.
If a disorder has hundreds of thousands of repeats, it can be detected with _______
Coding region
Southern Blot
T/F
Minors are only tested for disorders occurring in childhood
True
What major disorder is due to a missense mutation - one AA for another?
Sickle Cell Anemia
Would a pt with know sickle cell go through chromosome analysis?
No.
Cause knows - no need
Different mutations, same locus, similar phenotype:
Different phenotypes, mutations in same gene:
Different mutations, different gene (locus), similar phenotype:
Different expressions of mutant allele:
Allelic heterogeneity
Clinical heterogeneity
Locus heterogeneity
Variable expressivity
