Intro 7/30 Flashcards
One DNA Double Helix
One chromosom,e (before replication
karyotype
the number and visual appearance of the chromosomes in the cell nuclei of an organism;
lymphocyte B cell DNA are used in humans
Dosage of a gene
is the number of copies of a particular gene present in a genome (one chromosome line is one dosage. Homologous chromosomes have a gene dosage of 2)
Colchicine
inhibits microtubule polymerization by binding to tubulin. Spindle poison. Used in karyotyping to keep sister chromatids together in metaphase
Giemsa-trypsin
Dye and protease used in karyotyping. Trypsin digests proteins (histones) to isolate DNA. Stain dyes DNA- banding pattern on chromosomes.
Types of genetic diseases
chromosome disorders, single gene disorders, mitochondrial disorders, multifactorial disorders
Chromosomal disorders
abnormalities in the number or structure of chromosomes (i.e. too many genes, too few genes, altered genes) Polyploidy, aneuploidy, insertion, deletions, translocations
Polyploidy
in humans, having a multiple of 23 total chromosomes, common in cancers
Aneuploidy
1 extra chromosome overall
single gene disorders
alterations in the coding sequence produce effects on the function of the protein (usually loss, but can be gain or alteration of function)
- DNA coding for mRNA but also tRNA, rRNA, snRNA, miRNA
- Autosomal disorders and sex-linked disorders
Mitochondrial genome contains 13 genes that encode for
Electron transport chain (production of ATP)
Mitochondrial disorders
maternal inheritance for mutations in mitochondrial DNA
can have same mutations as on chromosomal disorders
multifactorial disorders
most common of genetics disorders and probably diseases
combo of both genes and the environment: polygenic, teratogenic, multifactorial
Polygenic
many genes acting together
Teratogens
chemicals in the environment that cause developmental deformities in babies.
Chronic myelogenous leukemia
inherited leukemia. Caused by Chromosome 22/chromosome 9 translocation. Causes fusion of Bcr/Abl portions of genes. (called Philadelphia chromosome)
Tools for genetic diagnosis
inheritance patterns (autosomal or sex-linked: pedigree), chromosome analysis (karyotyping, FISH, CGH), biochemical tests (plasma amino acids, urine organic acids), DNA diagnostic tests (whole genome sequencing)
Autosomal dominant pedigree
somebody is affected every generation
both males and females are affected
Karyotyping
detects alteration in number: large duplication/deletions, translocations
FISH (fluorescent in-situ hybridization)
used to check specific DNA sequence portion of known diseases. Performed on cells frozen in metaphase. Fluoresces target gene after the cell is washed and is hybridized by the tagged single strand DNA sequence
-if the probe hybridized to the sample, the DNA sequence is present (ex. Williams syndrome. Chromosome 7 band present in one chromosome). -tests for deletions and duplications
CGH (comparative genomic hybridization) AKA Chromosomal microarray
- checks for deletions/insertions (duplications) in genome
- the DNA of the patient is compared to a reference DNA of a healthy person
- metaphase slide is prepared and frozen, DNA is removed, chromosomes are fluoresced.
- patient DNA is green
- Reference/control DNA is red
- If red on array plate- this portion of DNA is deleted in the Patient
- if Green on array plate, this portion of DNA is duplicated
- if yellow, the DNA sequence of the certain part is the same as the control DNA
- ex. Williams syndrome. Chromosome 7 band present in one chromosome
Plasma amino acid test
can detect Phenylketonuria (loss of PAH activity resulting in accumulation of phenylalanine)
Presymptomatic testing
testing a person for a genetic mutation that will CERTAINLY cause a disease later in life (i.e. Huntington’s disease and familiar adenomatous colon cancer)
Predisposition testing
testing a person for a genetic mutation which MIGHT cause a disease later in life
Mosaicism
more than one genotype in a person
Mitochondrial inheritance
abnormal mitochondria passed on in the cytoplasm of an ovum from mother
Genetic imprinting
parent-of-origin difference in gene expression
Uniparental disomy
both chromosomes of a pair inherited from one parent
Unstable triplet repeat mutations
develop by expansion of normally present trinucleotide repeats
