2. Genetics and disease 1 Flashcards
1. Discuss the major types of human genetic diseases and their patterns of inheritance. 2. Outline the methods used to clone genes responsible for inherited human diseases. 3. describe the cloning of genes for selected inheritance diseases and how this explains the pathogenesis of these diseases. 4. discuss the practical applications of genetic studies for diagnosis and treatment.
what are some germline defeats?
- chromosomal defects
- mitochondrial disorders
- Monogenic disorders
- polygenic disorders
what are some somatic defects?
- Cancers
- Mosaics
- Chimeras
what cells do germline defects effect?
germline cells before fertilisation
what cells do somatic defects effect?
any cell after fertilisation
what are the most common genetic disorders?
somatic diseases especially cancer
how common are germline disorders?
not uncommon generally about 1 in 20 people
what do we mean when we refer to genotype?
- the genetic make up of the organism including nuclear and mitochondrial DNA
- it reflects the DNA sequence of the genome
what do we mean when we refer to phenotype?
- the physical characteristics of the organism
- these can be observed, detected or measured
how is most genetic material organised?
into chromosomes
how many chromosomes do humans have?
23 diploid pairs = 46 individual chromosomes
what is classical or forwards genetics?
identifying the underlying genetic cause of a given phenotype using techniques such as genome-wide association studies
- work from the disease phenotype back to the genetic cause
what is reverse genetics?
finding the function of a known gene.
done by altering gene expression using knock-out, knock-down or over expression as well as mutagenesis
look for the end phenotype and disease
what is positional cloning?
Identifying a gene based on chromosomal location
what was positional cloning before the genome project?
- identify a chromosomal abnormality
- generate genetic and physical maps
- breakdown into contigs
- find the candidate genes
- mutation detection
what was positional cloning after the genome project?
whole genome mapping was a lot easier and chromosomal contigs
then genome sequencing to find the candidate gene
then mutation detection
what is linkage analysis?
- aims to identify genetic loci that are inherited together more often then by chance
- mainly use polymorphic markers that are known and can be tested
- co-inherited polymorphic markers can give a specific loci from which we can look for candidate genes
what is linkage analysis good for?
identifying traits that are strongly influence by a single gene
monogenic disorders
what are genome wide association studies good for identifying?
more complex traits caused by polygenic disorders
what is the principle behind linkage analysis?
the closer 2 genes physically on the chromosome the more likely they are to be inherited together
what are the 2 genes used in linkage analysis?
the candidate gene for the disease in question
the polymorphic marker that is tagged and identifiable
how is mapping done using linkage analysis?
markers 1 million bp apart have 1% recombination frequency = 1 centimorgan
measure linkage using the LOD score
LOD>3 indicates linkage
what are some common polymorphic markers?
- Restriction fragment length polymorphisms
- variable number tandem repeats (mini satellites)
- microsatellites
- single nucleotide polymorphisms
what are Restriction fragment length polymorphisms?
single point mutations that cause the addition or loss of a restriction site
commonly used
what are variable number tandem repeats (mini satellites)?
repeats of 20-30bp with a varying number of repeats
when run on a gel a large band indicated lots of repeats
what are micro satellites?
Di, Tri and tetra nucleotide repeats
often linked with certain diseases
what are single nucleotide polymorphisms?
single base changes that occur around every 300 bases
each SNP has a 1% frequency in the population
gene mapping: pre-genome project
- develop regional genetic maps but you have to start in kind of the right area
- use markers to select genomic clones
- produce a contig which is a complete clone map of a region
- search for genes
what methods were used to search for genes pre-genome project?
CpG islands
Zoo blots
northern blots
cDNA library screening
Exon trapping
cDNA selection