Final Review Flashcards
Fragile X repeat/location:
CGG in 5’ UTR
Huntington Disease repeat/location:
CAG-coding disorder in exon
Freidreich Ataxia repeat/location:
GAA in intron; only autosomal recessive disorder
Myotonic Dystrophy repeat/location:
CTG in 3’ UTR
Achondroplasia Inheritance
AD or incomplete dominant
Achondroplasia Mutations
One mutation accounts for majority of
mutations; most (80%) are de novo (ALWAYS on paternal allele)
Achondroplasia Diagnosis
PCR followed by restriction enzyme digestion
p.Gly17Arg:
missense mutation
p.Gly17
nonsense mutation
p.Leu6Hisfs*3
frameshift mutation
101-2A>T
Splicing mutation in intron
+at beginning of intron
-at end of intron
Certain genes are only expressed from one parent
Imprinting
Inheritance of both alleles from one parent
Uniparental Disomy
What’s a risk in during MII in older moms?
chromosomal nondisjunction
Average size of a gene?
14,000 bp or 14 kb (22,000 genes in genome)
What is 1 cM equivalent to?
1,000,000 bp or 1000 kb or 1 Mb
Different phenotypes result from mutations in the same gene
Clinical Heterogeneity
Different mutations in the same gene cause the
same phenotype
ALLELIC HETEROGENEITY
Mutations in different genes give same phenotype
Locus Heterogeneity
where a single gene may cause multiple phenotypic expressions or disorders.
pleiotropy
Production of same phenotype by different genetic mechanism
Genetic Heterogeneity
an altered gene product that acts antagonistically to the wild-type allele
Dominant Negative
What is the underlying molecular mechanism for type I OI with DI?
Dominant Negative
In what disorder does nondisjunction always occur in male meiosis II?
47, XYY
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. How many chromosomes does she have?
45
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%
The woman with the baby 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.
A woman and her brother are carriers of a balanced Robertsonian translocation between chromosomes 14 and 21. Who has the highest risk to have a child with Down syndrome?
Risk is always higher to a female.
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.
Thinking about Turner syndrome: How many are spontantously aborted?
99%
What is unique about Turner syndrome?
Only viable monosomy in humans
Thinking about Turner syndrome: What would the karyotype show?
45, X
How many codons total?
64
How many stop codons, and what are they?
3: UAA, UAG, UGA
Is the code the same for nuclear and mitochondrial DNA?
No
Characteristics of Non-penetrance
Affected parent and child while themselves unaffected
How can a female have an X-linked recessive disorder?
Skewed X activation (most likely) Assortative mating Consanguinity Uniparental disomy Turner’s Syndrome
Most common mechanism that causes PWS?
Paternal 15q11q13 deletion
Most common mechanism that causes Angelman’s?
Maternal 15q11q13 deletion
What is the most efficient method for testing for PWS and AS?
Methylation analysis
Uniparental disomy has implications for which types of disorders?
Imprinting disorders
Recessive disorders
What are the components of a PCR?
Template Primer DNA polymerase Nucleotides Buffer (magnesium)
Autosomal dominant Mechanisms of action
Haploinsufficiency
Dominant negative
Gain of function
where a diploid organism has only a single functional copy of a gene (with the other copy inactivated by mutation) and the single functional copy of the gene does not produce enough gene product (typically a protein)
Haploinsufficiency
Number of PCR cycles required to generate 1 million copies?
20
Number of PCR cycles required to generate 1 million copies?
20
45, XX, t(14;21) Phenotypically normal?
Normal Female with a balanced translocation between 14 and 21
46, XX Phenotypically normal?
Normal Female
45, X Phenotypically normal?
Turner Syndrome
46, XY Phenotypically normal?
Normal Male
47, XXY Phenotypically normal?
Klinefelter Syndrome
Tall, sterile male
Why would someone have a karyotype performed?
growth/ development problems
Dysmorphic features
stillbirth/ neonatal death
Male and female fertility issues
Family history of chromosome abnormalities
Neoplasia
Pregnancy in women of advanced maternal age
What is the underlying mechanism for type I OI with DI?
Dominant negative: the mutant protein action is overriding normal protein action
Describe Triploidy
69 chromosomes
Mechanism: fertilization of one ovum by 2 sperms
Babies are born, but don’t live long
Describe Tetraploidy
92 chromosomes Karyotype is 92 XXXX or 92 XXYY Mechanism: failure to complete early cleavage division of a zygote Embryos, but no babies 3x less common than Triploidy
Phenotype produced by exposure to an environmental agent and looks like a genetic disorder
Phenocopy
Define Polygenic
Multiple genes contribute to phenotype, usually each with a small contribution
Important in complex traits like diabetes
When Genes and environment contribute to phenotype
Multifactorial
What bill was passed to try and prevent genetic discrimination in obtaining a job and health insurance?
Genetic Information Nondiscrimination Act (GINA)
True or False? Robertsonian translocations are translocations between two metacentric chromosomes.
FALSE. They are between two acrocentric chromosomes.
True or False? Balanced translocation carriers are not at risk to have unbalanced offspring.
FALSE
True or False? Of the gametes that a carrier of a 14;21 Robertsonian translocation can make, ½ are not viable.
TRUE. Those that end up with monosomy 21, monosomy 14, and trisomy 14 are not viable.
True or False? In a female with a translocation between an autosome and the X chromosome, the normal X will be preferentially inactivated.
TRUE
the best examples in humans of diseases Imprinting
PWS and AS
Achondroplasia Mutation
FGFR3 mutation
Example of Synergistic heterozygosity
epigenetic factors, and environmental influences may combine with specific genetic mutations to produce
nonsyndromic clefting
Chromosome with Centromere in the center of the chromosome
Metacentric
Chromosome with Centromere slightly towards one end
Submetacentric
Centromere at one end
Acrocentric
How long does male gametogenesis last?
Lasts 60-65 days, but continues through life
spermatids ejaculated per ejaculation?
100-200 Million, If your Me about 800million
5’UTR=
untranslated region “upstream”
3’UTR=
end “Downstream”
How many amino acids have only 1 codon?
2, Methionine (AUG) and Tryptophan (UGG)
Autosomal Recessive Diseases to remember
Sickle Cell Anemia
Cystic Fibrosis
Amelogenesis Imperfecta
Autosomal Dominant Diseases to remember
Achondroplasia
Neurofibromatosis
Amelogenesis Imperfecta
Hereditary Gingival Fibromatosis
Protein does something it doesn’t normally
do (or does its usual job better)
Gain of Function
Myotonic Dystrophy Mechanism of disorder
Mechanism of disorder : Non-coding repeat
CTG repeat in 3’ UTR
Affected have >50 repeats
Anticipation noted
Diagnosis in neonates with Myotonic Dystrophy Mechanism of disorder
Hypotonia Facial muscle weakness Generalized weakness Club foot Respiratory insufficiency or failure
Diagnosis in adults with Myotonic Dystrophy Mechanism of disorder
Muscle weakness of distal leg, hand, neck, and face
Myotonia
Cataracts
Myotonic Dystrophy Mechanism of disorder Inheritance
Most always inherited from mother, but also possible from father
All known polyglutamine disorders are characterized by …
progressive neuronal dysfunction that typically begins mid-life, resulting in severe neurodegeneration
Hutchinson-Gilford Progeria
Due to a de novo mutation
gly→ ser
Affects splicing: new cryptic splice site
DNA probes specific for individual chromosomes, chromosomal regions, or genes used to rapidly diagnose abnormal chromosome number or deletions/insertions
Fluorescence In Situ Hybridization (FISH)
Number of PCR cycles required for
accumulation of specific amt of product
is a reflection of relative amt of nucleic
acid template present in sample
Taqman
Or Quantitative PCR
measure the accumulation of PCR product
during the course of the reaction (“real-
time PCR”)
translocation between the long arms of 2 acrocentric chromosomes
Robertsonian Translocation:
Compulsive eating, developmental delay
PWS
Seizures, ataxia, inability to talk
AS
Number of PCR cycles required for
accumulation of specific amt of product
is a reflection of relative amt of nucleic
acid template present in sample
Taqman Test
