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
MEN syndromes follow an autosomal dominant pattern of inheritance. MEN-2A and MEN-2B are both linked to distinct mutations in the
ret proto-oncogene.
Like MEN-2A, MEN-2B is also characterized by pheochromocytoma and medullary carcinoma of the thyroid. But unlike MEN2A, MEN2B is also associated with
marfanoid habitus
ganglioneuromas (GI/mouth)
Mutations in ___have been associated with papillary carcinoma of the thyroid. This is the most common thyroid malignancy, and it has been associated with a remote history of radiation exposure
BRAF
The _____ mutation is associated with follicular thyroid carcinoma
RAS oncogene
caused by a genetic defect in the NADPH oxidase enzyme, resulting in impaired phagocytosis. These patients are especially susceptible to infections with catalase-positive bacteria and fungal organisms such as Aspergillus, Nocardia, Serratia, and Staphylococcus aureus, among others.
Chronic granulomatous disease (CGD)
CGD is inherited in an ____ manner.
X-linked recessive
(X-linked skewed in girls)
Infant with a flank mass
Wilm’s Tumor (WT1) Kindey
or
Neuroblastoma (n-myc) Adrenal Gland
Presents with no symptoms or fever and weight loss in advanced disease.
Can also present with abdominal or back pain, constipation, opsoclonus myoclonus syndrome, or unexplained secretory diarrhea due to paraneoplastic production of vasoactive intestinal polypeptide (VIP)
Neuroblastoma
Colon cancer is associated with 4 mutations.
KRAS, RAF, p53, and APC
Chromosome count for
Turner Syndrome
Kleinfelter Syndrome
Turner Syndrome – 45, XO
Kleinfelter Syndrome – 47, XXY
Down Syndrome – 47, Trisomy __
Edwards Syndrome – 47, Trisomy __
Patau Syndrome – 47, Trisomy __
21
18
13
one gene causes multiple pheontypic effects (a lot of things wrong with someone)
Pleiotropy
Ex: PKU
Increased severity or earlier onset of disease in next generation
Anticipation
ex: Huntington
Mutation in tumor suppressor gene must occur in both copies of the allele to cause cancer unlike mutations in oncogene allele where one bad copy is enough to cause cancer.
Loss of Heterozygosity
Ex: Retinoblastoma, Lynch syndrome, Li-Fraumeni
Heterodisomy indicates meiosis __ error
Isodisomy indicates meiosis __ error
I (hetero)
II (Iso/homo)
Prader willi occurs when ____ gene is deleted/mutated
Paternal
Seizures
Ataxia
Intellectually disabled
Laughter (randomly)
Angelmann
Hyperphagic
Fat (obsese)
Retarded
Micropenis (hypogonadism)
Hypotonia
Prader Willi
Myopathy
Lactic Acidosis
CNS disease (stroke-like episodes)
failed oxidative phosphorylation
Ragged Red Muscle fibers
Mitochondrial Myopathy
(MELAS syndrome)
Cell death in optic Nerve neurons
Subacute bilateral vision loss in teens/ young adult
Males (90%)
mitochondrial inheritance
Leber Hereditary Optic Neuropathy
Autosomal Dominant Diseases
(14)
Achondriplasia
PKD
FAP
Familial Hypercholesteremia
Hemorrhagic Telengiectasia (Osler-Weber)
Huntington
Marfan
NF 1/2
MEN 1/2
VHL
Tuberous Sclerosis
Myotonic Muscular Dystrophy
Li-Fraumeni
Hereditary Spherocytosis
Autosomal Recessive Diseases
(11)
Albinism
Glycogen Storage Diseases
AR-PKD
CF
Freidrich Ataxia
Hemochromatosis
Kartagener
PKU
Sickle Cell Anemia (Thalassemias)
Sphingolipidoses (Not Fabry)
Wilson’s
CFTR gene on Chromosome
7
CFTR encodes an ATP gated _______:
What does it do?
Chloride channel that secretes Cl- into the lung and GI lumens
but reabsorbs Cl in the sweat glands
Where is the Misfolded protein product of CFTR retained in the cell?
What happens as a result to Cl- and Na+?
RER
↑ Cl- in the cell
↑ Na+ reabsorption
Water follow Na+ into the cell instead of staying in the lumen mucus causing thick secretions.
In CF ↑ Na+ reabsoption causes a more ____ transepithelial potential difference
Negative
Reticular nodular pattern on CXR
Opacification of Sinuses
Steatorrhea
in a caucasion child
CF
List some complications of CF
(around 10)
Recurrent Pulm Infections (ABPA, Pseudomonas)
Chronic Bronchitis/ Bronchiectasis/ COPD
Pancreatic Insufficiency/ Steatorrhea/ Malabsorption
Fat Vitamin (ADEK) deficiency
Biliary Cirrhosis
Liver Cirrhosis
Infertility (no Vas Deference, but OK spermatogenesis)
Ammenorhea (low fertility)
Nasal Polyps
Clubbing nails
What drug slows CF disease progression
Ibuprofen
Used for Phenylalanine deletion in CF patients:
- Corrects misfolded protein and improves translocation to cell surface
- Opens Cl- channels for improved Cl transport
- Lumacaftor
- Ivacaftor
XLR disorders
(10)
Orinthine Transcarbamylase Deficiency
Fabry
Wiskott Aldrich
Ocular Albinism
G6PD deficiency
Hunter Syndrome
Burton agammaglobinemia
Hemophilia A/B
Lesch-Nyan
Duchenne/Becker
Fragile X Syndrome is inherited in what fashion
XLD
Caused by De-novo sporadic mutation mostly in girls
Rett Syndrome
List the 4 Tri-Nucleotide Repeat diseases
*Bonus if you can remember the repeat sequence
Huntington (CAG)
Myotonic Dystrophy (CTG)
Fragile X (CGG)
Freidrich Ataxia (GAA)
Try Hunting My Fragile Freedom
Loss of motor/ verbal/ cognitive skills
Ataxia
Seizures
Growth failure
Hand Wringing
Girl
Rett syndrome
Most common inherited cause of intellectual disability
Fragile X
*Down’s is the most common genetic cause
Fragile X FMR1 gene is ____ thus it has ↓ expression
Hypermethylation
Long Face
Large Jaw
Mitral Valve Prolapse
Large Testes
Hypermobile Joints
Big Everted Ears
Autistic/ Mentally Retarded
Fragile X Syndrome
FXS Trinucleotide expansion occurs during
oogenesis
Most common cause of death in Duchenne Muscular Dystrophy is
Cardiomyopathy
Helps anchor muscle fibers in skeletal and cardiac muscle
Dystrophin
↑ CK
↑ Aldolase
+/- Myonecrosis
Calf Pseudohypertrophy
Use Upper Extremities to stand (Gower’s)
Duchenne Muscular Dystrophy
(FRAME SHIFT deletion)
Non-frameshift deletion of dystrophin gene causes truncated protein
Becker’s
(onset in teen years)
Cataracts (eye problems)
Early Balding
Testicular atrophy
muscle wasting
arrythmias
Myotonic Distrophy
Abnormal expression of myotin protein kinase causing myotonia ( difficulty releasing hand from grip)
causes muscle wasting
and arrythmias
Myotonic Dystrophy
(CTG of DMPK gene)
Cataracts, Toupee balding, Gonadal atrophy
Robertsonian Translocation:
Long arms of 2 ___ chromosomes fuse at the centromere and the 2 short arms are lost.
Down Syndrome from fusion of Chromosomes: __ & __
acrocentric
14 & 21
*receiving 14 & 21 short arm fusion = death in utereo
Low hCG
Low/– Inhibin
Low alpha-feto protein
Trisonomy 18 Edwards
Men 2A disorders
Parathyroids
Pheochromocytoma
Medullary Thyroid Cancer
Men 2B disorders
Gliomas
Pheochromocytoma
Medullary Thyroid Cancer
Disorders by Chromosome
3
5
7
9
13
17
22
3: VHL, RCC
5: FAP, Cri-du-Chat
7: William’s, CF
9: Friedrich Ataxia, Tuberous Sclerosis
13: Wilson’s , Patau, Retinoblastoma, BRCA2
17: NF1, BRCA1, TP53
22: NF2, DiGeorge
myoclonic seizures and myopathy associated with exercise. Skeletal muscle biopsy shows irregularly shaped muscle fibers (ragged red fibers)
Inheritance pattern
Myoclonic epilepsy
Mitochondrial Inheritance
XLD diseases (2)
FXS
Rett
The TATA and CAAT boxes are ___ in eukaryotic cells and are located approximately 25 and 75 bases upstream from the transcription start site, respectively.
promoters of transcription
The Kozak consensus sequence plays a major role in initiation of the eukaryotic ___ process.
translation
Both the ___ box and the ___ box promote initiation of transcription by acting as binding sites for general transcription factors and RNA polymerase II.
CAAT
TATA
Genomic ____ is caused by DNA methylation, an epigenetic process in which genes can be silenced by attaching methyl groups to cytosine residues in the DNA molecule.
imprinting
The ___ is added as a post-transcriptional modification downstream of the consensus sequence (AAUAAA) located near the 3’ end of the mRNA molecule. It protects mRNA from degradation within the cytoplasm after it exits the nucleus.
poly-A tail
Telomeres are located at the ends of chromosomes and contain TTAGGG repeats, which are added by the enzyme
telomerase (RNA-dependent DNA polymerase).
Short non-coding RNA sequences (eg, microRNA and small interfering RNA) induce posttranscriptional gene ___ by base-pairing with complementary sequences within target mRNA molecules.
silencing
___ factors recognize stop codons (eg, UAA, UAG, and UGA) and terminate protein synthesis. They facilitate release of the polypeptide chain from the ribosome and dissolution of the ribosome-mRNA complex.
Releasing
Splicing is a post-transcriptional modification in which introns are removed from pre-mRNA via
small nuclear ribonucleoproteins (snRNPs).
__ factors facilitate tRNA binding and the translocation steps of protein synthesis.
Elongation
tRNA has a ___ sequence at its 3’-end that is used as a recognition sequence by proteins. The 3’ terminal hydroxyl group of the A codon serves as the amino acid binding site.
CCA
The T loop contains the TΨC sequence that is necessary for binding of tRNA to ____. The TΨC sequence refers to the presence of ribothymidine, pseudouridine, and cytidine residues.
ribosomes
Some of the Genetic Code’s degeneracy is explained by the wobble hypothesis, which states that the first 2 nucleotide positions on the mRNA codon require traditional (Watson-Crick) base pairing, whereas the third “wobble” nucleotide position may undergo ____ base pairing.
less stringent (nontraditional)
All ribosomal RNA except 5S rRNA is transcribed in the
nucleolus
The nucleolus is the site of ribosomal subunit maturation and assembly. ____ enzyme functions exclusively within the nucleolus
RNA polymerase I
Enhancers and ____ may be located upstream, downstream, or within a transcribed gene; these gene sequences function to increase and decrease the rate of transcription, respectively.
silencers
Promoter sequences directly bind general ____ factors and RNA polymerase II upstream from the gene locus, which is necessary for the initiation of transcription
transcription
In contrast to promoters, ____ sequences bind activator proteins that facilitate bending of DNA. DNA bending allows activator proteins to interact with general transcription factors and RNA polymerase II at the promoter, increasing the rate of transcription
enhancer
The D loop contains numerous dihydrouridine residues, which are modified bases often present in tRNA. The D loop (along with the acceptor stem and anticodon loop) facilitates correct tRNA recognition by the proper _____
aminoacyl tRNA synthetase
Cytoplasmic ___ play an important role in mRNA translation regulation and mRNA degradation.
P bodies
Splicing is performed by spliceosomes, which remove introns containing GU at the 5’ splice site and AG at the 3’ splice site. Splice site mutations may result in inappropriate removal of exons and retention of introns, leading to the formation of ____ proteins.
dysfunctional
Homeobox genes encode DNA-binding transcription factors that play an important role in the segmental organization of the embryo along the ____ axis.
cranio-caudal
*Sonic Headgehog = Elongation (Proximal to Distal axis)
Translation of the mRNA template proceeds in the __ direction.
5’ to 3’
during translation tRNA anticodons will be oriented in the opposite ___ direction.
3’ to 5’
Stop codons (UAA, UAG, and UGA) halt protein synthesis by binding a ___ factor; they do not add amino acids to the polypeptide chain.
release
