Flashcards in Epigenetics and Imprinting Deck (46):
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)
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
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.
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.
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
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?
Which population has a higher rate of sickle cell?
Which ethnic group has a higher rate of cystic fibrosis?
Which group has a higher rate of Tay-Sachs disease?
Which populations have a higher relate of a-and-b thalassemia
People who live in areas with endemic malaria
Contains three copies of each chromosome (69 total)
Contain four copies of each chromosome. Lethal. 92 total chromosomes
Loss of a chromosome. Not compatible with life except for in the sex chromosomes
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.
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.
Patau syndrome. Least compatible to life. Nondisjunction during oogenesis. Polydactyl, cleft life and palate, small eyes, microcephaly, intellectual disability, and cardiac anomalies.
45, X. Nondisjunction during meiosis. X chromosome Monosomy. Short, webbed neck, no puberty, no secondary sex characteristics, streak ovaries. Female phenotype.
What does mosaicism indicate?
XXY. Nondisjunction during meiosis. Symptoms include testicular atrophy, gynecomastia (enlargement of male breasts), female distribution of hair, and infertility.
When is nondisjunction the most common?
In meiosis I in female
Balanced Chromosoma; Abnormality
No gain or loss of genetic material
Unbalanced Chromosomal Abnormality
Gain or loss of genetic material
Exchange of genetic material between non-homologous chromosomes
Typical Mendelian segreation where you get a normal gamete and a translocation carrier. Good segreation.
Bad segregation which would lead to spontaneous abortion
Translocation 9;22 which results in the activation of ABL protooncogenes which leads to chronic myeloid leukemia
translocation between chromosomes 13, 14, 15, 21, or 22 leading one chromosome to disappear resulting in a derived chromosome from the translocation between acrocentric chromosomes. The short arm is lost
What does robertsonian translocation usually lead to?
Large micro deletion (>4 Mb) syndromes
Wolf-Hirschhorn (4 p) and cri du chat (5 p)
Chromosome 5p loses some genetic material. Features include high-pitched, cat like cry, severe intellectual disability, speed problems, and microcephaly
What tests are best for Cri-du-chat
Fish or CGH
What micro deletion disorder is most common in humans?
Deletion of 4p. Facial anomalies with widely spaced eyes, prominent nose, and abnormal iris. Cardiac issues, intellectual and developmental delay.
Small micro deletions in 11p13. Wilms tumor, aniridia, genitourinary malformations, and growth and development issues
Involve the centromere
Does not involve the centromere
Can you see inversions using karyotype analysis?
Yes, because they change the banding pattern
Loss of one arm of a chromosome and duplication of the other arm. Results in chromosomal and gene dosage imbalance.