Variations on Mendel Flashcards
“Common” genetic variant
Minor allele frequency >/= 1%
ChIP Seq utilizes. . .
antibodies that recognize specific histone modifications.
5-methylcytosine
Methylation is a mechanism to silence a DNA region by directly inhibiting RNA polymerase machinery from binding. Usually occurs in CpG islands.
Of note, 5-methylcytosine, if deaminated, becomes thymine, and so is the most frequently mutated nucleotide.
Maintenance methylation
Most methylation is reset at. . .
gametogenesis
iPS cells
Induced pluripotent stem cells
Created by adding readers and erasers to remove chromatin modifications and cytosine methylations from DNA.
Maternal Imprinting Pattern Inheritance
Effect on transcription depends on whether it is inherited from the mother or father!
Many imprinted genes have. . .
non-coding RNAs
Beckwith-Wiedeman syndrome
Seen when a mutation causes a loss of proper imprinting at the IGF2 region and only when it is inherited from the mother, as shown in the pedigree. The disease is probably due at least in part to overexpression of IGF2 – in the absence of normal imprinting, the IGF2 gene is expressed from both chromosomes rather than just one.
Prader-Willi syndrome
The disease is often caused by a deletion of a particular imprinted region on chromosome 15, which contains a number of different genes (including noncoding RNAs) that are only expressed from either the maternal or paternal chromosome. The same deletion can cause either Angelman syndrome or Prader-Willi syndrome, depending on whether the deletion is passed on by a mother or a father.
Prader-Willi’s is caused by maternal imprinting.
Angelman syndrome
Angelman syndrome is phenotypically very different from Prader-Willi syndrome but remarkably also results from a deletion of the same region on chromosome 15. In fact. the same deletion can cause either Angelman syndrome or Prader-Willi syndrome, depending on whether the deletion is passed on by a mother or a father. The fact that the same mutation in the same family can cause very different syndromes, depending on whether they are maternally or paternally inherited, provided strong evidence that these diseases are diseases of imprinting.
Angelman’s is caused by paternal imprinting.
Uniparental Disomy
Unparental disomy leads to normal expression of most genes, but altered expression in imprinted regions. Uniparental disomy also increases the risk of “regular” Mendelian disease, since it is effectively a form of consanguineity.
Lyon hypothesis
XX individuals are actually genetic mosaics.
The process is called “Lyonization”
Some incomplete penetrance of low expressivity in X-linked diseases in females may be due to. . .
Differential X-inactivation
Four S’s of genetic disease
Transposable Elements and Hemophilia
Some cases of hemophilia A are caused by an insertion of a transposable element in the coding sequence of the Factor VIII gene.
Fukuyama-type congenital muscular dystrophy
The insertion of a transposable element in the 3’ UTR of the fukutin gene decreases gene expression and causes a type of muscular dystrophy.
RNA editing
In very rare cases (more common in plants, but also documented in humans), RNA may be edited in order to convert cytidine into uridine or adenosine into inosine, changing how the RNA is read.
Diabetes is usually ____ in origin
polygenic
Mostly common noncoding variants
Most of the time, DNA methylation is similar between chromosome pairs – either both the maternally- and paternally-derived chromosomes are methylated or both are unmethylated. It turns out that the presence of methylation at certain sites in the ABC7 gene is correlated with decreased expression of the gene.
What would you find if you analyzed the patterns of methylation at these sites in ABC7 in a healthy individual without any ABC7 mutation? How about in a healthy individual from the Darwin family carrying the deletion in ABC7?
In a case of maternal imprinting, . . .
In a case of maternal imprinting, the paternal copy will be expressed!!!!
Pseudoautosomal region
Region of a barr body that escapes X-inactivation.
