Genetics Flashcards by Stephanie Escobar

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

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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)

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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

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People are sick with same disease, but some are more/less sick than others

Phenotype varies among individuals with same genotype/disease

Variable Expression

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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)

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People are sick with similar/same disease but have completely different mutated genes/chromosomes

Locus Heterogenicity

ex: Albinism

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Relative amount of normal vs. mutated mitochondria inherited from mother

Heteroplasmy

*Type of Variable Expression

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missense vs. nonsense mutation in the same gene, but demonstrating different severity

Allelic heterogenicity

*Type of Variable expression

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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

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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

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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)

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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)

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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

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Structural Abnormalities in chromosomes like non-disjunction or translocations best visualized via

Karyotyping

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Structural Abnormalities like Deletions best visualized via

Fluorescence in situ hybridization (FISH)

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During ______ of spermatogenesis and oogenesis, homologous chromosomes “trade” DNA → genetic diversity of offspring.

prophase I

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Unbalanced trading of genes in meiosis 1 (prophase 1)

(during homologous recombination)

causes:

chromosomal deletions

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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)

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Most common Congenital metal retardation

Down’s

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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)

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High hCG

High Inhibin A

Low alpha-feto protein

Nucal Transluscency

Down Syndrome Trisonomy 21

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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

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Mental Retardation

microphthalmia (small eyes)

microcephaly

cleft lip/palate

holoprosencephaly

polydactyly

VSD

cystic kidneys

Patau

Non-Disjunction Trisonomy 13

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microcephaly

moderate to severe mental retardation

epicanthal folds

VSD

high pitched cry

Cri-Du Chat

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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 migratio_**n 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: ## Footnote \_\_ 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

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

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: 1. Corrects misfolded protein and improves translocation to cell surface 2. Opens Cl- channels for improved Cl transport

1. Lumacaftor 2. 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) **C**ataracts, **T**oupee balding, **G**onadal 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, BRCA**2** **17**: NF**1**, BRCA**1**, TP53 **22**: NF**2**, 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.

CC**A**

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

Genetics Flashcards

(127 cards)