Genetics Flashcards
What are the 4 Steps (Questions) to determining what the Inheritance pattern is?
-
Mitochondrial, If Yes. (If no, move on)
- Does a sick mom have all sick kids: Yes
- Does a sick dad have no sick kids: Yes
-
Does the sick kid(s) have a sick parent?
- If yes → Dominant
- If no → Recessive
- If Yes to Q2
- has dad given it to sons? If yes, Autosomal
- has dad given it to only daughters? if yes, XLD
- If No to Q2
- Are mostly males affected? If yes, XLR
- Are both genders affected? if yes, autosomal
How to go about determining is someone is a carrier?
The less you know about an individual the more possibilities there are to divide from (ie 4)
The more you know the less possibilities there are to divide from (ie 1-3)
Example: How likely is an unaffected person with an affected sibling, likely to be a carrier for a autosomal recessive?
Based on Punnet Square
AA 25%
Aa 50 % (Carrier)
aa 25% (affected)
BUT we know this person is unaffected so we can elimnate the aa 25% box
so we are left with
AA 1/3 = 33%
Aa 2/3 = 67% (Brother has 67% chance of being carrier)
How to calculate recurrence risk knowing gender in an XLR disease?
From a basic punnet square of XX/XY we know
50% XX
50% XY
If previous soon is affected then we know forsure mom is the carrier since dad can’t give the son an X
Thus X0X/ XY results in
25% X0Y 25% XY
25% X0X 25% XX
But we know baby is female so we can eliminate XY & X0Y possibilities
leaving 50% → X0X genotype probability
People are sick with same disease, but some are more/less sick than others
Phenotype varies among individuals with same genotype/disease
Variable Expression
Some people have the mutation but show NO signs of sickness, while some do
Incomplete penetrance
Will affect recurrence risk (Phenotypic risk = probability of genotype * probability of penetrance)
People are sick with similar/same disease but have completely different mutated genes/chromosomes
Locus Heterogenicity
ex: Albinism
Relative amount of normal vs. mutated mitochondria inherited from mother
Heteroplasmy
*Type of Variable Expression
missense vs. nonsense mutation in the same gene, but demonstrating different severity
Allelic heterogenicity
*Type of Variable expression
Certain genes are only active if they are transmitted from the appropriate parent.
- During gametogenesis, methylation (inactivation) of specific genes occurs in sperm and in eggs.
- Women imprint (inactivate) the _____ gene.
- Men provide a copy of the imprinted gene unless it was deleted during gametogenesis (_______ phase of meiosis)
- Men imprint (inactivate) the _____ gene.
Prader-Willi
prophase I of meiosis
Angelman
Rare condition where both chromosomes carrying a certain gene are given by only one parent.
Can be another cause of prader-willi/angelman
Uniparental disomy
*random event = reccurence risk almost 0
Sperm or egg undergo
nondisjunction during development
(incorrect separation of chromosomes during meiosis)
List 5 examples
aneuploidy
Turner Syndrome – 45, XO
Down Syndrome – 47, Trisomy 21
Edwards Syndrome – 47, Trisomy 18
Patau Syndrome – 47, Trisomy 13
Kleinfelter Syndrome – 47, XXY
( i KEPTD the chromosome)
what 2 forms of euploidy are not viable (compatible with life)
Triploid – 3 copies of each, 69 total – non-viable
Tetraploid – 4 copies of each (92 total) – non-viable
(too many sperm fertilized one egg)
Non- Disjunction during Meiosis 1 occurs when ______ were supposed to separate during metaphase 1.
Non-Disjunction during Meiosis 2 occurs when _______ were supposed to separate during metaphase 2.
Where is non-disjunction most likely to occur?
Homologs
Sister chromatids
most likely to occur in Meiosis 1
Structural Abnormalities in chromosomes like non-disjunction or translocations best visualized via
Karyotyping
Structural Abnormalities like Deletions best visualized via
Fluorescence in situ hybridization (FISH)
During ______ of spermatogenesis and oogenesis, homologous chromosomes “trade” DNA → genetic diversity of offspring.
prophase I
Unbalanced trading of genes in meiosis 1 (prophase 1)
(during homologous recombination)
causes:
chromosomal deletions
list 4 examples of Interstitial (middle) deletions
and
1 example of Terminal deletions
*bonus if you can also recall the chromosome:)
Interstitial (middle) deletions:
Prader-Willi and Angelman syndromes (Chromosome 15q)
DiGeorge syndrome (Chromosome 22q)
Wilms tumor (Chromosome 11p)
Williams syndrome (Chromosome 7q)
(Why Wait, Please Delete)
Terminal deletions:
Cri-du-chat syndrome (Chromosome 5p)
Most common Congenital metal retardation
Down’s
List (6-ish) associated illnesses for DOWN syndrome
(Trust me this comes up in ALL practice exams)
ASD/VSD
Alzehimers
AML/ALL
Hirschsprung
Duodenal Atresia (vomit + double bubble)
Heart Defects (endocardial cusion and AV canal)
High hCG
High Inhibin A
Low alpha-feto protein
Nucal Transluscency
Down Syndrome Trisonomy 21
mental retardation
rocker-bottom feet
small jaw (micrognathia)
low-set ears
clenched hands with overlapping fingers
prominent occiput
congenital heart disease (VSD)
Edwards
Trisonomy 18
non-disjunction
Mental Retardation
microphthalmia (small eyes)
microcephaly
cleft lip/palate
holoprosencephaly
polydactyly
VSD
cystic kidneys
Patau
Non-Disjunction Trisonomy 13
microcephaly
moderate to severe mental retardation
epicanthal folds
VSD
high pitched cry
Cri-Du Chat
what anomaly causes cri-du-chat
microdeletion of short arm of chromosome 5
mental retardation
hypercalcemia
↑ sensitivity to Vitamin D
musical talent
supravalvular aortic stenosis
well-developed verbal skills
extreme friendliness with strangers
Williams
what cause Williams
microdeletion of long arm of chromosome 7
APT7B gene region lost includes elastin gene
abnormal embryological development of 3rd and 4th pharyngeal pouch and Defective neural crest migration to these pouches caused by
microdeletion at chromosome 22q11
- Catch 22 disease
- DiGeroge
Dysmorphic facial features include orbital hypertelorism (widely spaced eyes), short palpebral fissures and short philtrum, cleft palate, and bifid uvula.
DiGeorge
Conotruncal cardiac defects (Tof etc.)
Thymic hypoplasia/aplasia (T-cell deficiency)
Craniofacial deformities (cleft palate)
Hypocalcemia/Hypoparathyroidism
DI George
(Palate, Face, Heart problems)
CATCH-22 disease
refers to DiGeorge whats it stand for
cleft palate
abnormal facies
T-cell deficiency (thymic aplasia)
cardiac abnormalities
hypocalcemia (parathyroid aplasia= tetany)
Huntington’s can present with a grimace or other involuntary facial movements. How does Anticipation occur?
During spermatogenesis, CAG repeats in the abnormal HTT gene (chromosome 4p) can rapidly increase
Hunter’s think ANTICIPATION always. ALWAYS
Two allele loci are said to be in ____ when a pair of alleles are inherited together in the same gamete (haplotype) more often or less often than would be expected given random pairing.
linkage disequilibrium
This most often occurs when the genes are in close physical proximity on the same chromosome.
aka Observe Frequencey >> Expected frequency
3 causes of Down
Non-disjunction
Robertsonian Translocation
Mosaicism
Duschenne Muscular Dystrophy is caused by frameshift mutations (most common) or ____ mutations in the dystrophin gene that lead to the formation of a truncated, defective protein.
nonsense
Frameshift mutations alter the reading frame of the genetic code, resulting in the formation of nonfunctional proteins.
How is the Gel Electrophoresis affected
If it causes the gene to be shorter than the band will move further down the gel
Inheritance:
Leber hereditary optic neuropathy
Rett syndrome
Huntington’s
Hemophilia
Galactosemia
mitochondrial inheritance disorder
XLD
AD
XLR
AR
A Child has a trisomy and is showing three bands on the Gel.
When did Non-disjunction occur
Meiosis I (3 bands)
Meiosis II (2 bands)
presents with myopathy (muscle weakness, myalgia), lactic acidosis due to impaired aerobic glycolysis, and nervous system dysfunction (neuropathy, seizures). Muscle biopsy classically shows ragged red fibers.
Inheritance Pattern
Mitochondrial Myopathy
Mitochondrial inheritance (all kids of affected mother have it)
Achondroplasia is an ____ disorder that results in a gain-of-function mutation in the FGFR3 gene.
autosomal dominant (AD)
Sickle cell anemia is an autosomal recessive disease.
Offspring of carrier parents have a ___ chance of being affected and a ___ chance of being heterozygous carriers, resulting in a ___chance of inheriting at least one mutant allele.
25%
50%
75%
____ describes instances where multiple phenotypic manifestations result from a single genetic mutation.
Pleiotropy
Ex) PKU
_____ refers to the differences in severity of autosomal dominant disorders.
Variable expressivity
some cells may have completely healthy mitochondria, while other cells contain mitochondria affected by genetic mutation
heteroplasmy
In siblings:
__ chance of inheriting all the same HLA genes (identical HLA match).
__ chance of inheriting half of the same HLA genes (haploidentical HLA match)
__ chance of inheriting none of the same HLA genes (HLA mismatch).
1/4
1/2
1/4
tuberous sclerosis and neurofibromatosis exhibit
Variable Expressivity
BRCA1 mutation is inherited in an _____pattern and exhibits a phenotypically variable presentation. This is called _______.
autosomal dominant
incomplete penetrance
(mutation does not always cause cancer)
_____ occurs when more than one set of genetic information is found within the gamete cells. A pedigree is shown.
Germline mosaicism
Ex: OI
The guanine-to-cytosine bond is stronger than the adenine-to-thymine bond because guanine and cytosine form
three hydrogen bonds,
3 Ps” Pituitary, Parathyroid, and Pancreas
Men 1
