Genetics Flashcards
____ are the foundation for all cellular structure and function
Proteins
How many genes in the human genome
50,000
What percent of DNA is used to make proteins?
10%
8% is regulatory and 2% is the actual code for the protein
Exons
Portion of gene that is transported out of the nucleus and translated into a protein
Different types of introns
Portion of gene removed from RNA transcript before translation.
- Non coding part
- No translation to protein (RNA splicing)
- Regulation of gene expression
What factors may effect transcription?
External factors such as toxins and medicine
Internal factors such as cytokines
Both can elicit or inhibit RNA transcription.
Epigenetics and examples
Extra-DNA modifications to the genome. Influences phenotype. Does not change the DNA sequence and is not encoded in the DNA sequence.
Examples of epigenetics that can affect genome
Chemical compounds. Methylation silences.
Can be inherited
Can be acquired by external factors such as diet, pollutants.
How does methylation affect the genome
It silences the gene. No transcription.
Autosome vs allosome
Autosome: Homologous pairs (1-22)
Allosome: Sex chromosomes (23)
How is DNA wound?
Double helix organized by histones into nucleosomes. Condensed into chromatin that make up chromatids.
Locus
Location of a gene/marker on a chromosome.
Diploid cells have ___ loci per gene
- One per chromosome
Allele:
Gene variant at a particular locus.
Homozygous vs heterozygous
Homo: Both alleles are the same on each gene locus.
Hetero: different alleles. Some genes have few alleles, other have thousands.
Non-mendelian genetics
Penetrance (complete and incomplete) and expressivity.
Both can be affected by lifestyle/environmental factors.
Penetrance
Likelihood of manifesting a particular phenotype given the same genotype.
Complete- everyone with the same genotype manifests the same phenotype.
Incomplete (variable)- 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.
Mendelian Inheritance (6 patterns of inheritance are observed)
Co-dominant Autosomal dominant Autosomal recessive X-linked dominant X- linked recessive Mitochondrial
Autosomal dominant disorder passing down rate
Each child has a 50% chance of inheriting the disorder.
Affects male and females in each generation
Ocular examples of autosomal dominant disorders
Retinitis Pigmentosa. Progressive vision loss.
Dominant Optic Atrophy. Progressive vision loss.
Retinoblastoma
Rb1 gene mutation.
90% of patients who have the gene will develop the condition.
Considered autosomal dominant with reduced penetrance.
Usually unilateral.
Autosomal recessive disorder passing down rate.
Each child has a 25% chance of being affected.
Both parents must be at least heterozygous (carriers) to transmit the disorder.
Appears equally in male and female children of unaffected parents.
Autosomal recessive disorder almost always associated with the _____ of the affected gene.
Loss of function.
Ocular examples of autosomal recessive
Retinitis pigmentosa
Congenital stationary night blindness
Sickle Cell disease
What kind of mutation is it?
Point mutation on chromosome 11 Missense mutation (1 change in BP)
What happens in patients that have sickle cell anemia?
Lowered levels of oxygen cause crisis.
Cells sickle and become sticky, blocking blood flow and can cause clot formation.
__% of african americans have sickle cell traits.
9
1 in 600 AA have sickle cell anemia.
Ocular manifestations of
Ischemia causes retinopathy
“sea fan” neovascularization
Vitreous hemorrhages
Retinal detachements
Codominant inheritance
One gene has more than one allele that can be expressed.
Phenotype is influenced by both inherited alleles.
Ex: ABO locus
X-linked dominant disorders inheritance
Affected males pass the disorder to all daughters, but no sons.
Affected heterozygous female pass condition down to half their sons and daughters.
Ocular example of x linked dominant disorder
Ocular albinism
Fragile X syndrome
Tri-nucleotide repeat disorder Variable penetrance Variable expression -males express more than females -Ocular manifestations (strabismus and refractive errors)
X-linked recessive disorders affect males or females more?
Males. Asymptomatic female carriers transmit the disorder to 50% of their male offspring.
Ex: red-green colorblindness. Retinitis pigmentosa.
X linked ocular disorders
Red-green color blindness.
Congenital stationary night blindness.
Retinitis pigmentosa
Choroideremia- nyctalopia
Mitochondrial inheritance disorders
Only passed down by mothers.
Disorders appear in every generation of a family
Males = females, but expressivity can change between males and females. Usually affects males more.
Ex: lebers Hereditary optic neuropathy (Apoptosis of RGC)
Chromosomal disorders. When do they occur?
Reflect events that occur at the time of meiosis as gametes are being formed.
Ex: Nondisjunction or breakage of chromosome with loss or translocation of genetic material (translocation/deletion)
Two types of nondisjunction
Results in unequal separation of chromosomes during meiosis (chromosomal disorders) or mitosis (mosaicism). Manifestations will be different for each.
Results of nondisjunction
Results in 22 or 24 chromosomes in the egg or sperm.
Turner syndrome: 22 + 23 = 45 chr
Down Syndrome: 24 + 23 = 47 chr
Karyotype
Family photograph of chromosomes
Ocular manifestations of down syndrome
Epicanthic folds
Brushfield spots (circle around iris)
Refractive error
Early onset cataracts
Klinefelter’s syndrome
Nondisjunction of sex chromosome (23)
Person ends up with 47 chromosomes (XXY)
How to diagnose Klinefelters syndrome
One barr body (condensation of one of the X chromosomes)
Signs and symptoms of Klinefelters
XXY.
Phenotypical male.
Hypogonadism. Female secondary sex characteristics at puberty.
Turner Syndrome
Non-disjunction of 23
45, X karyotype.
Most common monosomy
Turner syndrome. 45, X
Signs and symptoms of X
Short stature, shield chest, webbed neck, reproductive sterile. Heart and kidney defects.
Ocular manifestations of Turners syndrome
45, X
Many binocular vision problems.
Chromosomal translocation
Transfer of chromosome parts between non-homologous chromosomes.
Robertson translocation
Unbalanced chromosomal translocation. Unequal parts of chromosomes are exchanged.
Additional cause of down syndrome.
Example of chromosomal deletion
Cri du chat syndrome. Loss of the short arm of Chromosome 5.
Two chromosomal deletions that affect the eye
WAGR (chr 11- aniridia)
Retinoblastoma (chr 13 deletion) Due to loss of tumor suppressor gene.
Ocular manifestations of Cri-du-chat syndrome
Hypertelorism- broadly spaced eyes
Epicanthal folds
Down slanting palpebral fissures
Strabismus
Hypertelorism
Broadly spaced eyes. Seen in Cri du chat syndrome.
Mosaicism
Could be due to non-disjunction or point mutations during mitosis. After fertilization, but early in development.
Ex; heterochromia.
Polygenic/multigenic disordres
Disease incidence is affected by multiple genes in addition to lifestyle and environmental factors.
