mab 11.1-11.3

Models of human diseases

-genetic diseases occur in model organisms

-we share many common genes w/ yeast, flies, etc

-check effectiveness and safety in preclinical studies before clinical trials in humans

-gene knockout mice for experiments

homologue

genes in species that are similar to human genes based on DNA sequence

OB mice

-mice = obese if they lack OB gene

-OB gene codes for leptin that controls hunger

-childhood obesity

what is apoptosis?

cell programmed death

apoptosis diseases

-neurodegenerative diseases (Alzheimer's, ALS, Parkinson's) too much apoptosis

biomarker

typically proteins produced by diseased tissue or proteins whose production is increased when a tissue is diseased

Example of biomarker

PSA (prostate-specific antigen) is released into bloodstream when prostate gland is inflamed. shows prostate inflammation or prostate cancer

2 body fluids biomarkers are released into

blood & urine

ctDNA

circulating tumor DNA, tumors give off DNA into bloodstream. Used to detect cancer. High levels can also predict survival.

Human Genome Project

-revealed all diseased genes on all human chromosomes

-prior: 100 genetic diseases, now: 2000 diseases

-chromosome maps (karyotypes) pinpoint locations of normal and disease genes of interest

amniocentesis

A technique of prenatal diagnosis (16 weeks) in which amniotic fluid, obtained by aspiration from a needle , is analyzed to detect certain genetic and congenital defects in the fetus with a karyotype.

chorionic villus sampling CVS)

fetus is 8-10 weeks

-remove a small portion of a layer of cell called the chorionic villus (fetal tissue that helps form the placenta), create karyotype

Restriction Fragment Length Polymorphisms to detect genetic diseases

-mutations mostly happen in specific genes, not abnormalities in chromosome numbers

-detective gene sequences may be cut differently by restriction enzymes than their normally bc nucleotide changes in the restriction site

EX: sickle cell disease

DNA microarray

silicon chips or microscope slides with DNA fragments that can allow many genes in a genome to be studied simultaneously

Karyotype

a type of chromosomal analysis that photographs and arranges chromosomes so that they can be visually inspected for defects

Allele specific oligonucleotide (ASO)

-mutation that doesn't change restriction site

- single nucleotide change in a gene

-DNA is isolated, then amplified, and probe with 2 different ASO's (one for normal gene, one for diseased gene)

Fluorescence in situ hybridization (FISH)

A procedure using a fluorescence-labeled probe to detect specific nucleotide sequences within intact cells attached to a microscopic slide

preimplantation genetic testing (PGT)

using ASO, PCR, and FISH to screen for genetic defects in the 8 to 32-cell-stage embryos prior to implantation

single nucleotide polymorphisms (SNP)

unique location where individuals differ by a single nucleotide

common form of genetic variation in humans

changes protein structure that produces diseases or influences traits in a variety of ways

predict susceptibilities to: stroke, cancer

Haplotype

groups of individuals that share the same SNP

Whole Genome Sequencing (WGS)

complete DNA sequence of an organism's genome at a single time; generating accurate reference genomes for microbial identification, and other comparative genomic studies

Whole Exome Sequencing (WES)

Genomic technique for sequencing all of the protein coding genes in the genome

Single-cell sequencing (SCS)

Technology that can provide DNA sequence information from a single cell as opposed to sequencing the genomes from a collection of cells

RNA-seq

Sequencing technique used to determine directly the nucleotide sequence of the RNA that is expressed within a population of cells

Single-cell RNA sequencing (scRNA-seq)

Sequencing RNA from a single cell, determine gene expression and heterogeneity of cell types

GWAS (genome wide association study)

a method for identifying chromosomal regions containing genes whose variation influences a disease phenotype by using millions of genetic markers scored for hundreds or thousands of individuals who have the disease and who do not have the disease