Meeting 19

diseae caused by mutation in single gene (IL2Rc gene)-gene makes sure differentiation of white blood cells happen correctly-when the gene is mutated, that cell can’t make cell lineges in differentiated form = immunodeficiency-example of a gene where gene therapy works-take the gene, put into retroviral vector, infect stem cells with virus, and then inject stem cells in blood ---- stem cells go on to create proper lineages-b/c it’s a retroviral vector gene is inserted into genome – in some cases this can cause cancer (inserted into region you don’t want to disrupt: causes over-proliferation and subsequently leukemia

• reverse genetics
• -reverse: known protein/gene causing disease, insert 'fixed copy' back into organism is gene therapy; taking a gene in a testube and going back to the test tube

• forward: mutagenizing organisms, seeing how they affect organism
• CANNOT do forward genetics in hhumans (Can't mutagenize, can't force them to mate with anyone)

single gene is the genetic bases of the disease

when one bad copy of a gene located in an autosome (one of the 22 human chromosomes that aren't sex chromosomes) is DOMINANT and therefore expressed in a heterozygote (ex. huntington’s); usually one parent has the disease (symptoms don't manifest until after reproductive age)

recesi=sive allele on the x-chromosome will mostly be expressed in males; mothers are phenotypically normal and act as carriers; need two bad copies on the x-chromosome

both parents must be heterozygous carriers of the allele in order for their children to be at risk for the disease; needs both copies of the recessive allele from each parent (ex. cystic fibrosis)

autosomal dominant

autosomal recessive

carrier versus incidence frequency

small population that either increases or stays the same and has a basis of this defect: the members of this population share these bad genes = increased risk of genetic disease (all of us have bad genes)

Nicher; collected WBC's within used/collected bandages

gene therapy; rescue analysis only comes later when you know what gene you're talking about

you'd see two bands on the gel; in someone who's HOMOZYGOUS, you'd only see one band because they have two copies of the same gene

differences among individuals in the sequence of genomic DNA that create or destroy sites recognized by particular restriction enzymes; are one of several types of sequence differences between individuals that can serve as DNA-based molecular markers in human linkage studies

see how A cuts two different lengths? that shows up on a gel, because of the RFLP; this can be a phenotype just like CyO can be or whatever; here you're just tracking a molecule; B (there's no RFLP), so the bands are the same size and just come out as the same length on the gel

some place in the genome where you might have one letter or a different one; RFLP's can be SNPs but not always (for example if there was a deletion not replacement)

LOT'S of SNPs aren't RFLPs

can test for these using: can sequence it (PCR) around that position and then sequence the DNA; need to know the sequence in general to find the surrounding area (that will hopefully stay the same, can be used to make the probes)

also microarray: big enough it's unique, but not too big that it overwhelms the discrepancy; if you get the temperature just right, there will only be hybridization with the one that matches EXACTLY; the others will not hybridize

some different number of repeats of some small sequence; mutates rapidly because the polymerase tends to slip

to test: PCR...then run a gel, primers that are out here, you'll get something shorter or longer depending on the number of repeats there are

short, tandemly repeated sequences that are found at centromeres and telomeres as well as at other chromosomal locations and are not transcribed; also called satellite DNA??

bacterial artificial chromosome; big plasmid

places where the markers are; knowing there can be differences in individuals between markers

autosomal dominant mutation; when looking at families, you find markers that are associated with people who have the disease

mutations in any one of multiple different genes can cause the same disease

alleles of multiple genes, acting together within an individual contribute to both the occurence and the severity of disease