Imprinting and Epigenetics Flashcards
1
Q
Prader-Willi syndrome (PWS) and Angelman syndrome
A
- best known microdeletion syndromes
- by karyotype analysis, both appear to have the same interstitial deletion of the proximal long arm of the chromosome 15
- clinically very different
2
Q
Prader-Willi syndrome
A
- patients are small and hypotonic at birth, but change within the first year of life to gain weight rapidly
- if not placed on a controlled diet, they can become quite obese due to overeating
- other characteristics include small hands and feet, hypogonadism, and a bad temper
- although they are developmentally delayed, most do well in special education classes
- because of their temper and difficulty in controlling their diet, Prader-Willi patients may be placed in special group homes that provide the proper environment
3
Q
Angelman syndrome
A
- severly mentally retarded
- although they are friendly, they usually cannot carry on a normal conversation, and discourse if often punctuated by bursts of inappropriate laughter
- hyperactivity, short stature, microcephaly, seizures, and ataxia
4
Q
Tests to pick up Prader-Willi and Angelman
A
- Cytogenetics- Prader Willi 60-65% found, 10-20% Angelman cases
- FISH- 65-85% Prader Willi and Angelman
- Unknown 15-35% Prader Willi and Angelman
5
Q
Causes of Prader Willi
A
- deletion on the chromosome 15 inherited from the dad
- not all PWS patients have deletions, some PWS has two copies of the maternal chromosome 15 (maternal uniparental disomy)
6
Q
Causes of Angelman Syndrome
A
- deletion present on chromosome 15 inherited from the mom
- therefore, there appears to be a maternal vs. paternal origin difference in the two diseases
- often had two copies of a paternal chromosome 15
7
Q
Disomy vs Uniparental Disomy
A
- the presence of 2 chromosomes
- Uniparental Disomy: inheritance of a chromosome or chromosomes from 1 parent to the exclusion of the other parent
- this can’t be detected by karyotype because the homologs will look alike, has to be done using molecular probe technology
- furthermore, using molecular studies, it is possible to determine if the chromosomes are from different sources (heterodisomy) or are duplicate copies (isodisomy)
8
Q
Uniparental isodisomy vs uniparental heterodisomy
A
- uniparental isodomy- duplication of 1 chromosome from one parent reslting in the lack of heterozygosity
- uniparental heterodisomy- when there are 2 different chromosomes but both come from the same parent, nondisjunction errors
9
Q
Cystic Fibrosis
A
- mechanism has been confirmed by molecular analysis of patients
- given the relatively high frequency of CF carriers in the general population, it is not unusual for a couple with no family history
- it is unusual when the child has two copies of the F508 mutation, paternity is as stated and only one parent has that mutation
- if examination of both of the child’s chromosomes 7 reveals that he/she is homozygous at all loci on the 7, this is uniparental isodisomy
10
Q
Deleted trisomy
A
- some nondisjunction results in trisomy
- can be corrected if 1 of the 3 chromosomes is lost, this loss is randem
- 2/3 of time there is biparental heterodisomy, 1/3 time of uniparental heterodisomy
11
Q
Imprinting
A
-the differential modification of the maternal and paternal genetic contributions to the zygote resulting in the differential expression of parental alleles during development and is adult
12
Q
Imprinting: Male and Female Effect
A
- for some genes or chromosomal regions, it may be important to have a maternal and paternal contribution
- not all genes or all chromosomes
- usually associated with methylation which is an epigenetic modification
- imprinting-lasts one generation
- change occurs at meiosis
13
Q
Methylation
A
- addition of methyl groups to cytosine residues in the DNA
- can occur within a single gene or a group of adjacent genes
- can occur over a portion of a single chromosome
- can occur over the full length of one or more chromosomes
- the pattern of methylation can be different between males and females
14
Q
Meiotic Imprinting
A
- all humans are mosaics of chromosomes inherited from their mothers and fathers. A male will pass on male imprinted (or methylated) chromosomes, and a female will pass on female imprinted chromosomes
- although it is acceptable for the somatic cells to be a mosaic of male and female imprinted chromosome, at the time of reproduction, it is essential that the single correct imprint be transmitted to the offspring
- all male gametes need to carry male chromosomes and all female gametes must carry female chromosomes
- one of the functions of meiosis is to reimprint all of the chromosomes that will end up in gametes
- chromosomes in male meiosis will have the imprint stripped and replaced with a male imprint
- female with female
- thus a child should receive an equal allotment of male and female chromosomes
15
Q
Imprinting Failure
A
- this process could fail and as diagrammed from the male, some of the chromosomes would retain the female methylation pattern
- thus in the population of male gametes, on average, half would carry chromosomes with a female imprint
- it is therefore possible to have a child with one chromosome from dad and one chromosome from mom, but both chromosomes have a female imprint
