Genetics Flashcards
DNA:
- information storage material for ____
- structure: ____
- 4 paired nucleotide bases: _____
all organisms and many viruses;
double-stranded helix;
adenine-thymine, gaunine-cytosine
codon
triplet of DNA bases that code for a specific amino acid
amino acids are assembled into ____
proteins
proteins are the foundation for ____
all cellular structure and function
gene
- DNA sequence that codes for a protein
- basic operational unit of genetic information
____ genes in human genome
~50,000
_____% of DNA is used for making proteins:
- ____% is regulatory only
- ____% is the actual code for the protein
10;
8;
2
DNA is transcribed into _____ in the _____
RNA;
nucleus
RAN is translated into _____ in the _____
protein;
cytoplasm
exons
portions of gene translated into protein
intron
- portions of gene removed from RNA transcript before translation
- non-coding parts
- no translation to protein (RNA splicing)
- regulation of expression of genes
factors effecting transcription
- external or internal: cytokines/toxins/medicine
- can elicit or inhibit RNA transcription
epigenetics
- extra-DNA modifications to the genome
- chemical compounds that regulate DNA expression (e.g., methylation silences transcription)
- influence phenotype
- do not change the DNA sequence
- not encoded by the DNA sequence
- can be inherited and/or acquired by external factors (diet, pollutants, etc.)
epigenetics:
- fetal changes are ____
- environmental changes are _____
- preconception exposure of gametes affects _____
permanent;
temporary;
gene expression
genome
total collection of genetic information
chromosomes
- super-coiled storage structure for genes
- 46 chromosomes/23 pairs
diploid
2 copies of each chromosome
haploid
1 copy of each chromosome (gametes)
autosome
homologous pairs (chromosomes 1-22)
allosome
sex chromosomes (X and Y)
locus
- location of a gene/marker on the chromosome
- diploid cells have 2 loci per gene (one per chromosome)
allele
gene variant at a particular locus
homozygous
both alleles are the same
heterozygous
both alleles are different
genotype
“the code”; 2 alleles at the same locus
phenotype
“shine through”; expression of the code (ex: hair color, height, eye color, presence or absence of a disease)
penetrance
likelihood of manifesting a particular phenotype given the same genotype
complete penetrance
everyone with the same genotype manifests the same phenotype
incomplete penetrance
everyone has the same genotype, but some do not manifest the same phenotypes
expressivity
degree to which the phenotype is expressed
variable expressivity
degree of phenotype expression varies between individuals with the same genotype
penetrance and expressivity can both be affected by _____
lifestyle/environmental factors
Mendelian inheritance:
6 general patterns of inheritance
- co-dominant
- autosomal dominant
- autosomal recessive
- X-linked dominant
- X-linked recessive
- mitochondrial
Autosomal Dominant Disorders:
- affected males and females appear in ____ generation of the pedigree
- affected mothers and fathers can transmit the phenotype to _____
each;
both sons and daughters
Autosomal Dominant Disorders:
ocular examples
- Retinitis Pigmentosa: progressive vision loss
- Dominant Optic Atrophy: progressive vision loss
Retinoblastoma
- autosomal dominant disorder with “reduced penetrance”
- 90% of patients who inherit this gene will develop the condition
- Rb1 gene mutation
- usually unilateral
Autosomal Recessive Disorders:
- almost always associated with _____ of the affected gene
- both parents must be _____ to transmit the disorders
- disease appears _____ in male and female children of unaffected parents
the loss of function;
at least heterozygous;
equally
Autosomal Recessive Disorders:
systemic examples
- cystic fibrosis
- sickle cell disease
Sickle Cell Disease
- point mutation on chromosome 11
- “mis-sense” mutation changes amino acid sequence
- alters protein structure to hemoglobin-S
- HB-S (not bound) aggregates –> semisolid gel –> vascular occlusion
- lowered levels of oxygen cause “crises”
- cells sickle and become sticky, blocking blood flow
- clot formation all throughout body
Sickle Cell Disease epidemiology
- 9% of African Americans have “sickle cell trait” (heterozygous)
- 1 in 600 African Americans have sickle cell anemia (homozygous)
Sickle Cell Disease ocular manifestations
- ischemia causes retinopathy
- “sea fan” neovascularization
- vitreous hemorrhages
- retinal detachments
Autosomal Recessive Disorders:
ocular examples
- Retinitis pigmentosa
- Congenital stationary night blindness (rod dysfunction)
Co-dominant Inheritance:
- one gene has more than one allele that can ____
- each allele makes ____
- phenotype is influenced _____
- ex: ____
be expressed simultaneously;
a slightly different protein;
by both alleles;
ABO locus (i.e., blood type)
X-Linked Dominant Disorders:
- affected males pass the disorder ____
- affected heterozygous females mating with unaffected males pass the condition to _____
to all daughters but to none of their sons;
half their sons and daughters
X-Linked Dominant Disorders:
systemic example
Fragile-X syndrome
X-Linked Dominant Disorders:
ocular example
ocular alibinism
Fragile X-Syndrome
- tri-nucleotide repeat disorder
- variable penetrance
- variable expression (males > females)
- clinical findings: intellectual disability, physical changes (long face, large ears, hypotonia)
- ocular manifestations: strabismus and refractive errors
X-Linked Recessive Disorders
- affect more ____
- asymptomatic female carriers transmit the disorder to ____
- examples: _____
males than females;
50% of their male offspring;
hemophilia, red-green colorblindness, retinitis pigmentosa
X-Linked Ocular Disorders
- red-green color blindness
- blue cone monochromat
- congenital stationary night blindness
- retinitis pigmentosa (can also be autosomal dominant and others)
- choroideremia: nyctalopia (progressive degeneration of choriocapillaris which will cause progressive vision loss)
Mitochondrial Inheritance Disorders:
- applies to genes ____
- only passed by ____
- disorder appears in ____ generation of a family
- males __ females
- example: ____
in mitochondrial DNA; mother; every; =; Leber's Hereditary Optic Neuropathy
Leber’s Optic Neuropathy
- point mutation of mitochondrial DNA causing apoptosis of retinal ganglion cells (RGC)
- symptoms: bilateral acuity loss, dyschromatopisa, onset typically in early 20s
- expressivity and penetrance vary between sexes (males>females)
chromosomal disorders:
- reflect events that occur at _____
- occur from: ____
the time of meiosis as gametes are being formed;
nondisjunction (defective movement of an entire chromosome), breakage of a chromosome with loss or translocation of genetic material (translocation, deletion)
nondisjunction
- unequal separation of chromosomes during meiosis (chromosomal disorders) or mitosis (mosaicism)
- homologous chromosomes or sister chromatids do not separate properly (meiosis I or II)
- will have either two copies of a chromosome or no copies
- unification with normal haploid cells= trisomy or monosomy
- results in 22 or 24 chromosomes in the egg or sperm
trisomies
- 3 copies rather than 2 copies of a chromosome
- trisomy 21 is most common form (Down Syndrome)
monosomies
-1 copy rather than 2
Trisomy 21/Down Syndrome
- variable expressivity
- signs and symptoms: intellectual disability, simian crease, umbilical hernia, leukemia
- ocular manifestations: epicanthic folds, brushfield spots, refractive error, cataracts (early onset)
Klinefelter’s syndrome
- nondisjunction of #23 (47, XXY karyotype)
- phenotypically male
- signs and symptoms: learning disabilities, hypogonadism, female secondary sex characteristics at puberty (persistent gynecomastia, female hair distribution)
- one Barr body
Turner Syndrome
- most common monosomy
- nondisjunction of #23 (45, X karyotype)
- phenotypically female
- signs and symptoms: short stature, shield chest, webbed neck, reproductively sterile, heart and kidney defects
- ocular manifestations: many binocular vision problems
chromosomal translocation
-transfer of chromosome parts between nonhomologous chromosomes
balanced translocation
- equal pieces of chromosomes exchanged
- fragments remain functional
Robertsonian translocation
- “unbalanced”
- additional cause of Down Syndrome
chromosomal deletion
- loss of a portion of a chromosome
- intermediate deletions lead to disorders
- Cri du chat syndrome
- Eye: WAGR syndrome (chromsome 11, wilms tumor/aniridia/genital and mental dysfunction), Retinoblastoma (chromosome 13)
Cri-du-chat syndrome
- loss of the short arm of chromosome 5
- clinical findings: intellectual disability, cat-like cry, ventricular septal defect
- ocular manifestations: hypertelorism (broadly spaced eyes), epicanthal folds, down-slanting palpebral fissures, strabismus
mosaicism
- occurs during early mitosis
- two genetically different cell lines derived from a single fertilized egg
- due to: nondisjunction, point mutations
- ex: heterochromia
polygenic/multigenic disorders
- disease incidence is affected by multiple genes in addition to lifestyle and environmental factors
- examples: diabetes, heart disease, autoimmune disease, cancer, mental illness, refractive error, macular degeneration
