Genetics Flashcards
What is the functional unit of the genome? How is it regulated?
- Gene
- Transcription
Define transcriptome
Expressions of genes modified by external influences (acetylation, phosphorylation, etc.)
Define microbiome
Constellation of viruses, bacteria, and fungi that colonize various human tissues
How much of DNA is expressed?
- Only 10% (25,000 genes)
- Other 90% do not encode genes and may serve a structural role
What causes gene silencing?
Methylation of cytosine
What does methylation of cytosine result in?
Gene silencing
Define imprinting
Inherited methylation of certain genomic regions (e.g. silencing of one X chromosome in females)
How many codons are possible?
4 bases (4^3) = 64
Describe codons
- Triplet of bases (64 possible)
- Each codon specifies 1 of 20 different amino acids
Define degeneracy vs. ambiguity
- Multiple codons can specify 1 amino acid (degeneracy)
- BUT a codon will only encode 1 protein
What is the initiation codon?
AUG
What are the termination codons?
UAA
UAG
UGA
Among women in their 40s, more than 25% of all pregnancies are estimated to involve:
- Trisomic conception
- Vast majority of these spontaneously abort (only trisomy 13, 18, 21, and sex chromosome survive to term)
Describe trisomy 13
- Median survival 2.5 days (1 in 20 survive more than 6 months)
- Holoprosencephaly (forebrain fails to develop into hemispheres)
How do infants with trisomy 18 present?
Clenched fist with 2nd and 5th digits overlapping the 3rd and 4th
Describe Klinefelter Syndrome
47, XXY karyotype
How do males with Klinefelter present?
- Thin build, disproportionately long arms and legs
- Mostly normal intelligence
- Gynecomastia
- Testicular dysgenesis
- Taurodontism (enlargement of molar teeth)
What is Klinefelter with subnormal intelligence or mental retardation associated with?
Higher number of X chromosomes
What are the Klinefelter variants?
- 48, XXYY
- 48, XXXY
- 49, XXXYY
- 49, XXXXY
Describe XYY super male
- Nondisjunction at 2nd meiotic division (fertilization with 2 sperms would result in 69, XYY)
- Learning problems at school
- Delayed emotional maturity
Describe Turner Syndrome
- XO
- Short stature
- Ovarian failure w/high LH/FSH
- Webbed neck 2/2 lymphedema
- Ortho abnormalities
- Shield chest
- HTN
Webbed neck and shield neck indicates:
Turner Syndrome (XO)
Gynecomastia and testicular dysgenesis with normal intelligence indicates:
Klinefelter Syndrome
Describe XXX syndrome
Typically no unusual physical features/medical problems
Why are there usually no physical features/medical problems a/w XXX syndrome?
Inactivation of all but 1 X chromosome
Define silent mutation
No ultimate consequence
Define missense mutation
- Change occurs in a coding region and alters an amino acid
- May result in non-functional protein
Define nonsense mutation
- Reading frame alteration results in an abnormal protein segment
- Usually results in unstable or non-functional protein
Define penetrance
% of individuals having a particular genotype that EXPRESS the expected phenotype
Define full penetrance
The gene mutation for a disease always results in the phenotypic change (if you have the gene, you WILL develop the disease)
Define incomplete penetrance
Individuals with abnormal genotype who do NOT have the disease
What is a disease that exhibits age dependent penetrance?
Huntington’s (delay in the age of onset of expression - symptoms not usually seen until 30 or older)
Define penetrance vs. expression
- Penetrance = PERCENTAGE of people with particular genotype that show expected phenotype
- Expression = DEGREE to which a phenotypic characteristic is exhibited
What has a higher mutation rate - oogenesis or spermatogenesis?
Spermatogenesis
-30 cell divisions by puberty, 20 each year after
(whereas oogenesis only 20 cell divisions to complete)
Spermatogenesis and deleterious mutations?
Approx 1 in 10 sperm carries a new deleterious mutation
What is the Hardy-Weinberg equation?
For 2 alleles (A and a), frequency of the genotypes: p^2 + 2pq + q^2 = 1
What does p^2, 2pq, and q^2 refer to for Hardy-Weinberg equation?
p^2 = frequency of AA 2pq = frequency of Aa q^2 = frequency of aa
Define overdominance
Occurs when heterozygote has a higher fitness than either homozygote
Advantage of sickle cell trait to malaria
- RBCs don’t sickle in trait until reduced oxygen tension
- Malaria parasite reduces oxygen tension within the RBCs
- RBCs in these pts then sickle and reduce parasitic burden
Define epigenetics
- Study of heritable changes in gene expression or cellular phenotype
- Caused by mechanisms other than changes in underlying DNA sequence (e.g. DNA methylation or histone deacetylation)
Define genomic imprinting
Epigenetic process that involves methylation and histone modifications in order to achieve monoallelic gene expression w/o altering genetic sequence
What is Prader-Willi syndrome?
- Disruption/deletion short arm paternal chromosome 15
- Maternal chromosome 15 imprinted (SILENCED)
What is Angelman syndrome?
- Disruption/deletion short arm maternal chromosome 15
- Paternal chromosome 15 imprinted (silenced)
Which syndrome consists of a silenced (imprinted) paternal chromosome 15?
Angelman syndrome
Which syndrome consists of a silenced (imprinted) maternal chromosome 15?
Prader-Willi syndrome
What are examples of autosomal dominant conditions?
Huntington’s
Achondroplasia
PKD
How do X-linked recessive conditions show up in families?
- All are fully evident in males (only 1 X chromosome, no normal gene to compensate)
- Women are rarely affected (only if 2 copies of mutant allele)
- NO father to son transmission
- All daughters of affected male will be affected (since father only has 1 X to transmit)
How do Y-linked conditions show up in families?
- Affects only males
- Affected males ALWAYS have affected fathers
- All sons of affected male are affected
How is mitochondrial DNA inherited?
Exclusively through maternal line (only the ovum contributes mitochondria to offspring)
How do children with multifactorial inheritance present?
Most affected children have normal parents
How should an individual with a dominant trait be called?
“Obligate heterozygote”
-Should NOT be called carrier (reserved for recessive traits)
What is FISH used for?
Help detect DNA sequence deletions or excess chromsome material
Direct vs. indirect FISH
- Direct: probe contains fluorophore (faster)
- Indirect: extra step w/nonfluorescent hapten on probe
What should a mass genetic screening program fulfill?
- Tested disorder is prevalent and serious
- It can be pre-symptomatically impacted through lifestyle changes, meds, etc.
- Identification of risk does NOT result in undue discrimination/harm
How does hyperphenylalaninemia present?
- Severe mental retardation (IQ 30)
- Hyperactivity
- Seizures
- Light complexion
- Eczema
How to achieve best outcome of PKU?
Elimination diet started in 1st month
What is the primary basis of carcinogenesis?
Genetic alterations of cell regulatory systems
Genetic alterations of cell regulatory systems results in:
Carcinogenesis
Major classes of cancer genes
- Tumor suppressor genes
- Oncogenes
- DNA repair genes
Describe tumor suppressor genes
- Normally inhibit cellular proliferation
- Recessive properties (both copies must be inactivated)
Describe oncogenes
- Normally activate cellular proliferation
- Dominant properties (only one copy needs to be mutated to result in unregulated growth)
Describe DNA repair genes
- Involved in DNA repair mechanisms
- Defective genes means breaks are NOT repaired
What 3 elements are required for gene transfer?
- Vector
- Transgene (gene to be delivered)
- Relevant target cell
Define transduction of gene therapy
Donated DNA enters target cell, expresses the transgene
Define the human genome project
Determine complete sequence of the 3 billion DNA subunits (bases)
Purposes of mapping human genome
- Enhanced understanding of disease
- Detection of infectious pathogens
- Diagnostic testing accuracy
- Treatment of disease
What is GINA?
- Genetic Information Nondiscrimination Act
- Prohibits health insurers and employers from using your genetic info against you (for hiring, firing, promotions)
What are the exceptions to GINA?
- Does not apply to employers with less than 15 workers
- Covers health insurance but not life or long term care insurance
What is MicroSort?
- Way to determine gender for conception
- More effective for girls than boys
