Genetics Flashcards
(42 cards)
Define Genetics
Genetics is the study of heredity and the variations in inherited characteristics and dis- eases.
Define Epigenetics
epigenetics refers to the study of heritable processes that alter gene expression without changing the DNA sequence.
Define Alternate Splicing
Allows different isoforms of a particular protein to be expressed. Vascular endothelial growth factor and its receptors have various isoforms due to this mechanism.
What are the 4 distinct cell cycle phases
- G1 (growth, preparation for DNA synthesis) * S (DNA synthesis/chromosome replication) * G2 (growth, preparation for mitosis)
- M (mitosis and cytokinesis)
What are the phases of mitosis
- prophase (chromatin is condensed into chromosomes)
- metaphase (chromosomes align in the middle of the cell)
- anaphase (chromosomes split and migrate to opposite poles of the cell)
- telophase (2 daughter nuclei form at the poles of the cell)
Meiosis vs Mitosis
outcome of meiosis is 4 genetically unique haploid cells, whereas the outcome of mitosis is 2 genetically identical diploid cells.
Cell cycle checkpoints
- G1: transition from G1 to S * G2: transition from G2 to M
At the G1 checkpoint, cell size and the availability of nutrients and growth factors are assessed, and the cell is checked for DNA damage. After completion of this checkpoint, the cell is committed to proceeding with cell division; otherwise, it enters the quiescent G0 phase. Before the cycle progresses to the M phase, further inspection of the DNA occurs at the G2 checkpoint. If damaged DNA is detected at either checkpoint, it may be repaired, or programmed cell death (see the section Apoptosis) may be initiated.
Checkpoint regulation
occurs via a family of proteins known as cyclins and cyclin- dependent kinases (CDKs).
At the G1 checkpoint, CDK phosphorylation of proteins of the retinoblastoma (Rb) family facilitates downstream transcription in preparation for S phase. Tumor suppressor genes like the Rb family often have a role in regulation of the cell cycle, dysregulation of which can lead to cancer (see the section “Tumor suppressor genes”).
Non coding DNA
Noncoding DNA is composed of highly repetitive sequences, some of which include satellites, microsatellites, short interspersed elements (SINEs), and long interspersed elements (LINEs). The 300-base-pair (bp) Alu sequence, named after the re- striction enzyme used to identify it, is the repetitive DNA that appears most frequently. Noncoding DNA comprises introns, promoters, and other regions within chromosomes and mitochondria and is involved in regulating gene expression and exon splicing.
Transcription factors
There are numerous families of these genes, including the homeobox and paired box genes. PAX6 acts as a master control gene for the development of the eye, an example of the key role of transcription factors in embryogenesis.
Conditions associated with Transcription factor mutations
PAX2 mutations cause colobomas of the optic nerve and renal hypoplasia.
PAX3 mutations cause Waardenburg syndrome with dystopia canthorum (types WS1 and WS3).
PAX6 muta- tions are the basis of virtually all cases of aniridia, occasional cases of Peters anomaly, and several other rarer phenotypes, specifically autosomal dominant keratitis and dominant foveal hypoplasia.
Where does splicing of introns occur
Splicing takes place in specialized structures called spliceosomes, which are composed of RNA and proteins. Errors of splicing can lead to genetic disease. For example, mutations in proteins that are vital in splicing can cause retinitis pigmentosa (RP).
X- inactivation
The random permanent inactivation of 1 of the 2 X chromosomes in the female, result- ing in the lack of expression of the majority of genes on that chromosome, is a significant event during early development of the human embryo. The time of X-inactivation is not precisely known but is thought to vary over a period of several cell divisions during the blastocyst–gastrula transition. X-inactivation is also known as lyonization, after its dis- coverer, Mary Lyon. Lyonization affects the severity of the phenotype of several X-linked retinal conditions, such as RP and incontinentia pigmenti.
Imprinting
Genomic imprinting is a heritable yet reversible process by which a gene is modified, de- pending on which parent provides it. The mechanism is unclear but appears to operate at the chromatin organization level and involves heterochromatization and methylation of CpG (cytosine-phosphate-guanine) sites.
Prader-Willi mutation
deletion of the paternally derived 15q11–q13, resulting in the loss of this region’s normal contribution from the paternal line.
Angelman Syndrome
have a deletion of 15q11–q13, but from the maternally derived chromosome, resulting in loss of the maternal contribution.
DNA Repair
Damaged DNA sites are repaired chiefly by 2 mechanisms: excision repair and mismatch repair.
Guardian of the genome
p53 revents cells from proliferating if their DNA is irreparably damaged. Levels of p53 increase after UV or ionizing radiation exposure. The p53 gene inhibits DNA replication directly and binds with 1 of the RNA polymerase transcription factors, TFIIH. If the degree of damage is slight, increased production of p53 induces reversible cell arrest until DNA repair can take place. If DNA damage is too great or irreversible, p53 production is massively increased and apoptosis occurs, probably through stimulation of the expression of the BAX gene, whose product promotes apoptosis. Loss of p53 causes cells to fail to arrest in response to DNA damage, and these cells do not enter apoptosis. Thus, mutations of p53 predispose to tumorigenesis.
Ataxia telangiectasia
The gene mutated in ataxia-telangiectasia (Louis-Bar syndrome), a protein kinase called ATM, also appears to be integrally involved in DNA repair, possibly by inform- ing the cell of radiation damage. The ATM gene product associates with synaptonemal complexes, promotes chromosomal synapsis, and is required for meiosis. Individuals with ataxia-telangiectasia have a threefold greater risk of cancer.
Xeroderma pigmentosum
a severe condition in which the functions of enzymes that repair UV-damaged DNA are crippled. Patients with this condition typically have diffuse pigmented anomalies on their sun-exposed skin and are at high risk for basal cell and squamous cell carcinoma, as well as melanoma. Ocular surface cancers (squamous
cell carcinoma and melanoma) can also develop in affected patients.
Apoptosis
Apoptosis is the process of programmed cell death that occurs in multicellular organisms, in contrast to necrosis, a form of traumatic cell death that results from acute cellular injury.Morphological changes include cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation.
Mutations vs Polymorphisms
Mutations are changes in DNA that can lead to disease, whereas polymorphisms are variations in DNA that were previously thought to rarely cause disease.
Mutations
can involve a change in a single base pair; simple deletion or insertion of DNA material; or more complex rearrangements such as inversions, duplications, or translocations.
Deletion/Insertion mutation of DNA
Deletion, insertion, or duplication of any number of base pairs in other than groups of 3 creates a frameshift in the entire DNA sequence downstream, resulting in the eventual formation of a stop codon and truncation of the message.