Epigenetics and Imprinting Flashcards
Epigenetics
A change in the expression of a gene that changes the phenotype without permanently changing the gene itself, but changes the chromatin structure. heritable change.
When is epigenetic repression very important?
In cell differentiation during embryonic development because it restricts access to certain genes
What does DNA methylation involve?
The addition of a methyl to the 5’ position of a cytosine by DNA methyl transferase
What are the steps involved in methylation inheritance and transcriptional repression?
1) Dnmt3 methylates unmethylated DNA
2) MeCP2 recruits either HDAC1 or Dnmt1
3) HDAC1 deacteylates histones
4) DNmt1 methylates hemimethylated DNA (1 strand is methylated, 1 isn’t)
Deacteylation
Removing of the negatively charges methyl group, which makes chromosomes more active
what is a really common form of methylation>
DNA methylation of globin genes in embryonic human blood stem cells which activates/inactivates different forms of the globin genes
ICF
Mutation in the Dnmt3b gene which is required for the initial methylation of unmethylated DNA. Symptoms include facial dysmorphisms, mental retardation, infection, immune deficiency. Rare autosomal recessive. Centromere instability of chromosomes 1,9, and 16.
Rhett Syndrome
X linked skewed inaction that is only found in girls. Loss of speech and acquired hand skills. Seizures, hand wringing, irregular breathing, and motor control problems. Caused by a mutation in the MeCP2.
Genetic Imprinting
Gamete of origin dependent modification of phenotype. origin of allele determines if that allele will be expressed. Can appear with recessive or dominant inheritance patterns. Occurs during gametogenesis.
Beckwith-Widemann Syndrome (BWS)
Enlarged tonight, higher birth weight, umbilical hernia, easy creates or pits, increased risk of cancer. Causes: maternal chromosomal rearrangements of 11p15, paternal disomy, and abnormal methylation at 11p15. Higher incidence in IVF babies
What genes have been shown to have abnormal methylation and lead to cancer?
Insulin like growth factor (IGF2) and IGF2 receptor
Incontienetia Pigmenti
Caused by a mutation of the X-linked IKBKG gene, which is lethal in males and has skewed X-inactivation in females
Which population has a higher rate of hemochromatosis?
Celtics
Which population has a higher rate of sickle cell?
African
Which ethnic group has a higher rate of cystic fibrosis?
Northern Europe
Which group has a higher rate of Tay-Sachs disease?
Ashkenzi Jews
Which populations have a higher relate of a-and-b thalassemia
People who live in areas with endemic malaria
Triploidy
Contains three copies of each chromosome (69 total)
Tetraploidy
Contain four copies of each chromosome. Lethal. 92 total chromosomes
Monosomy
Loss of a chromosome. Not compatible with life except for in the sex chromosomes
Trisomy 21
Most common. Down Syndrome. Most common caused is nondisjunction in meiosis I. Congenital heart defects, intellectual all disability, one crease in hand, short, early onset of Alzheimer’s.
Trisomy 18
Edward syndrome. Caused by nondisjunction during oogenesis. Features include clenched fist with overlapping fingers, rocker bottom feet, congenital heart defects, and intellectual disability. early death around 2 years old.
Trisomy 13
Patau syndrome. Least compatible to life. Nondisjunction during oogenesis. Polydactyl, cleft life and palate, small eyes, microcephaly, intellectual disability, and cardiac anomalies.
Turner Syndrome
45, X. Nondisjunction during meiosis. X chromosome Monosomy. Short, webbed neck, no puberty, no secondary sex characteristics, streak ovaries. Female phenotype.
