11/19 Genetics and Genetic testing. Flashcards
what is heritability
the proportion of variation in trait that is based on genes
what is the heritability of fat mass?
40-70%
why is obesity a mult-factorial trait?
it is affected by a large number of factors and a large number of different genes (probably more than a hundred)
What is the relationship between leptin and BMI
Directly related…but leptin doesn’t seem to be as effective in some people.
how does nicotine seem to affect appetite?
nicotine-arcuate nucleus nicotinic receptor-POMC neuron - MC4 receptors in secondary neurons reduce food intake and body weight
What is one way we can learn about common diseases by looking at small groups that inherit the traits mendilianly
there are many common diseases that have subtypes that have mendilian inheritance, and these can be studied to see what causes the phenotype.
what is the relationship between the severity of a disease causing allele and its frequency
inversely related. it seems that the alleles that most severly cause a common disease (the mendelian variations of a disease) are very rare.
What is a genome-wide assocation studies
look for varients (SNPs) that different in frequency in the population of cases and in controls…and these SNPs then are probably very close to causal allele.
How can you do genome-wide association studies
do DNA microarrays that will compare millions of DNA sequences on single chip!
what is the goal of genetic testing?
Detect mutations or other abnormalities that cause genetic disease in order to allow treatment and decision making
What Caveats should we consider when we approach genetic testing?
reveal mutaitons, but this does not mean that you will get a disease!! so the specificty is low! and- negative test result does not mean 0% risk of disease! For complex disease sensitivity and specificty are much lower!
What do I need to be able to do with genetics as a physician (at a min!)
When and why to order a genetic test and how to interpret the findings
how can we detect the transmission and presence of a disease causing allele without actually knowing what the mutation is?
use the principle of linkage with closely linked markers! we can fallow the markers and predict the presence of a mutation!
how can we make a direct genetic diagnosis of a patient
Use an electropherogram of a patient to check for the presence and number of an allele, or use a probe hybridization and microarray to check for the presence of a specific allele
what are the genes that we use to check for Breast cancer heritablility?
BRCA1 and BRCA2
how can we identify a mutation on an electropherogram (sanger sequence?)
look at the comparison of peak sizes and where there is a stark difference in peak height we have a mutation!
What is the difference in information that we need for direct vs. indirect genetic diagnosis?
Indirect [family information, errors possible by reombination, markers may be unimformative, can uncover multiple mutations]; Direct [ disease causing mutation must be known]
when do we use genetic testing?
prenatal; newborn; carrier testing; presymptomatic; testing for adverse drug reactioins; finding causes of undiagnosed diseases
Carrier screeening examples
Sickle-cell disease in African-American population; and Tay Sachs disease in Jewish population
How effective was genetic screening for Tay-Sachs in jewish populations?
The number of diseased individuals went to zero!!!
how do we undergo prenatal diagnosis of genetic diseases?
ultrasound; amniocentesis; chorionic villus sampling; preimplantation genetic diagnosis; diagnosis of fetal DNA in maternal circulation
How can an ultrasound be suggestive of down syndrome?
Nuchal translucency is increased in fetuses with trisomy 21…not diagnostic but suggestive!
what can you do with amniocentesis?
do karyotype, DNA testing, Alpha-fetoprotein level.
how safe is amniocentesis?
Fetal loss rate 1/500 above background
what is CVS for pregancy?
Chorionic vilus sampling: take a piece of Villus tissue and can get karyotype and DNA testing
Contrast the information gathered from CVS, Amniocentesis and Maternal Circulation tests
Amnio [Karyotype, DNA testing, Alpha-fetoprotein level]; CVS [Karyotype, DNA testing], [DNA testing, Karyotyping, esp. whole genome sequencing]
Constrast when you can perform CVS vs. Amniocentesis
CVS performed at 10-12 weeks gestation; Amniocentesis is performed at 16 weeks gestation.
what is the risk of CVS in pregnancy?
it is about 1/100 above background
what testing is done on IVF pregnancy?
preimplantation genetic diagnosis after in vitro fertilization. they take a cell from the fertilized embryo when it is only about 8 cells or so. and then can do in situ or SNP array or comparative genomic hybridization or PCR-based methods etc.
How can we do fetal DNA testing from the mom’s circulation?
1/1,000,000 cells in maternal circulation are of fetal origin, 5-50% of cel free DNA is of fetal origin. Diagnosis at seven weeks,
how effective is fetal DNA in maternal circulation testing for trisomy?
100% detection and 99.5% specificity
How much of the genetic information of the baby can we get from mother’s blood
we can do whole-genome sequencing of fetal DNA
What is the governments stand on genetic info
GINA prohibits discrimination by insurance companies or employies
What would a large jaw, with large ears and large gonads and low IQ suggest for genetic diseases?
it would suggest Fragile X
what type of inheritance would show more male affected, with not skipping generations
probably x-linked dominant with incomplete penetrance (fragile X is like this)
what is the equation for recombination rate?
with the marker and no disease divided by the #with the marker and with the disease
what does the LOD score tell us?
the high LOD means that the marker and the disease gene are probably linked closely together . High LOD is lclose on the same chromosome!
what is it called when subsequent generations have more severe symptoms?
antcipation – more and more copies of the disese causing mutation are present.
