9 28 Genetics-Table 1 Flashcards
what is genetic imprinting?
in imprinting the gene is inactivated (not transcribed) when transmitted by one of the two sexes: Aa is not equal to aA. therefore it matters if the gene is from the mother or from the father.
how does imprinting happen?
associated with methylation and chromatin condensaiton.
methylation and chromatin condenstiaon are both examples of?
epigenetic effects
symptoms of Prader-Willi Syndrome
Mild/mod. intellectual disability. Small hands/Feet; Hypogonadism; Obesity/hyperphagia; hypotonia;
what is parthenogenesis and why doesn’t it work?
an unfertilized egg (or egg w/ only paternal genes) gives rise to an offspring. this doesn’t work because of imprinting!
why does a parthenogenesis lead to a hyditiform mole?
if you get all the genes from dad, then because of imprinting you get many genes that simply aren’t active because of imprinting
what is the major cause of Prader-willi syndrome?
due to 4Mb deletion of chromosome 15q
summerized the idea of imprinting:
the sperm or overy silents specific sections of the gene during spermogenisist/oogenistis and this is passed to the offspring. therefore only the gene from one parent is active at all.
how do we get deletions or duplicates that are highly conserved i.e. the loss of 4Mb of chromosome 15q
unequal crossing over during meiosis
symptoms of angleman syndrome
severe intellectual disabilities; ataxia (characteristic gait and posture); seizures; spontaneous, uncontrolled laughter; 10% of cases due to 4Mb deletion of chromosome 15q.
how can the same deletion in the 4Mb region of 15q lead to two different diseases?
if get the deletion from the chromsome from dad, then you get prader-willi syndrome; if you get the deletion from mom, then you get angelman syndrome. that is because of imprinting.
what is the chromosomal explination for why loss of the same chromosome section can lead to either prader-willi or angelman?
in paternal chromosome you get the active PWS region gene in the maternal you get the active AS gene. the paternal has a silent AS gene and the maternal has a silent PWS region gene. therefore if you lose one or the other chromosome then you get either prader-willi or angelman.
what is the genelogical evidence for imprinting in PWS?
Mom who has PWS mated and passed on the deletion to the daughter, who had AS!
what is uniparental disomy?
one parent, two chromosomes: two copies of a chromosome inherited from one parent.
how can uniparental disomy happen?
this can happen from two chromosomes from dad and none from mom. or, two from one parent and one from another, and then lose one of the three and have only two maternal or two male chromosomes
if you had a uniparental disomy with two maternal chromosome 15s you get AS or PWS?
get AS!
symptoms of Bechwith-wiedemann
large size for gestational age; large tongue; increased incidence of wilms tumor, hepatoblastoma
what is the chomosomal explination for the large gestational size of Bechwith-wiedemann
usually IGF2 growth factor is imprinted in maternal chromosome to be inactive. If this imprinting is lost in the maternal chromosome then the maternal IGF2 is active and then over-express IGF2 and very large babies: Bechwith-wiedemann
Russel-silver syndrom
deficient IGF2 expression therefore short stature due to growth slowing
what is the general trend in imprinting of growth factors?
fathers tend to express genes that enhance fetal growth, and mothers tend to express genes that suppress fetal growth
what could be a cuase of Russel-silver syndrome?
the gain of imprinting in paternal gene for expression of IGF2?
Myotonic dystrophy
myotonia (can’t let go); loss of muscle tone; cardiac arrhythmia; testicular atrophy; cataracts; frontal baldness in males.
what is the inheritance type of myotonic dystrophy?
autosomal dominant condition
what is anticipation in an inherited condition?
the condition is seen earlier and earlier in each generation of the disease due to a lengthening of the tri-base repeat section
what cuases myotnic dystrophy
caused by expansion of a CTG repeat in the 3’ region of the DMPK. (this is an untranslated section of the gene)
how can a non-coding section of DNA cause Myotonic Dystrophy
abnormal mRNA interferes with RNA-binding protiens affecting splicing of other genes or a “toxic RNA” that compromises the RNA splicing of many genes.
what causes the “anticipation” in myotnic dystrophy
increasing size of the repeat in subsequent generations gives earlier onset
Symptoms of Fragile x syndrome
intellectual disability; behavioral disorders; large ears, jawas, macro-orchidism; joint hyperextensibility
what is the chromosme abnormality that cuases fragile x
the tips of the x chromosome has a very condensed region of DNA
why is the inheritance of fragile x through the generations see a higher rate of penetrance?
anticipation; or the increasing size of a non-coding tri-nucleotide expansion.
