Genetics 3 Flashcards
Meiosis happens when
All the time
What is happening with meiosis
Somatic cell division where a cell divides and both of the daughter cells are genetically identical
Accomplished by separating the identical halves of the chromosomes
Mitosis - is what
Pulls apart the chromatids - makes two identical cells from one mother cell
No genetic info is lost
Meiosis separates what
the homologous chromosomes - so we have reduced the genetic information per cell
Meiosis - time period when the maternal and paternal copes are in close proximity
Synapsis
There can be homologous recombination and bits from maternal can be switched to the paternal and you get new combinations
What are the steps in meiosis 1
Prohase/Metaphase Synapsis Crossover Anaphase (disjunction) Reduction division
After synapsis, what happens
Crossover - chance for error
After crossover, what happens
Anaphase disjunction - the chromosomes are separated and disjunction is when the spindle separates the homologous chromosomes and if this does not happen it is a non disjunction
After Anaphase/Disjunction - what happens
Reduction - reduced diploid and now we have haploid cells - equational division gives us 4 different haploid cells which is the major source of human variation
Chromosomal aberrations affect what
The expression of many genes
There are a lot of chromosomal aberrations but only some are compatible with life so we only see some out of the many that occur
Chromosomal aberrations can arise from
Unequal distribution of genetic material during meiosis I and II
Chromosome breaks that heal in an aberrant (incorrect) way
Chromosomal aberrations span more than just one system
You lose a bit of a chromosome and there are a lot of genes in there so this is why aberrations have a lot of different phenotypes
Chromosomal aberrations - How often do they occur
Frequently - in about 1 in 12 conceptions there is a detectable one
What is the most common cause of spontaneous aberrations
Chromosomal aberrations - 50%
Chromosomal aberrations - frequency at birth
1 in 150 live births have a detectable chromosomal aberration
Chromosomal aberrations - Deletion or duplication
Reduces gene dosage or increases it for a certain region
Chromosmal aberrations - Inversions
A bit breaks off and is being inserted back in opposite direction
Chromosomal aberrations - Insertion
Breaks off and is being inserted in center of another
Chromosomal aberrations - Translocation
Bits of chromosome of the end are breaking off and being exchanged with the end of another
Chromosomal aberrations - which can you usually live pretty well with
Insertions
Translocations
Inversions
No change in the amount of genetic material per cell - usually asymptomatic until next generation
Chromosomal aberrations - which are more serious
Deletion
Duplication
Genes that regulate development (haploinsufficiency) - Losing the second copy cannot be compensated for and have a third cannot either
Chromosome breaks - how do these happen
Common damage, both spontaneous and induced by environment
Chromosome breaks - how bad?
Are lethal to the cell if not repaired
Very important to repair even if repair is not done correctly though so can lead to translocation and possible abnormalities
Aberrant repair is rare but causes chromosomal abnormalities
Aberration - Deletion and Duplication - which is worse
Deletion of genetic material has more severe consequences than duplication
Aberration - deletion of a part of chromosome 5 results in
Cri du chat syndrome
Microcephaly, mental retardation, heart defect
Aberration - Translocations and Inversions
No genetic material lost, just rearranged (balanced alteration)
Aberration - Translocations and Inversions - symptoms
Mostly asymptomatic in the person who carries them but problems arise in the next generation when doing meiosis because you can get an imbalance
Aneuploidy - is what
We have extra or missing chromosomes
Aneuploidy - Arises from what
An error in meirosis (non disjunction)
One daughter cell receives both homologous chromosomes and the other receives none
Fertilization involving these gametes will lead to trisomy or monosomy
Aneuploidy - consequences
Very severe
Monosomy is lethal (except for X chrom)
Trisomy only observed in chrom 13, 18, 21 and the sex chromosomes
Trisomy 21 causes
Down syndrome and is the most commonly observed chromosomal aberration
NOT RARE
Sex chromosome Aneuploidies
Turner syndrome (45, X) Klinefelter syndrome (47, XXY) Klinefelter syndrome (48, XXXY)
Sex chromosome Aneuploidies - Turner syndrome
1 in 3000 F births
Sterility, short stature and other physical characteristics are observed
No mental retardation
Sex chromosome Aneuploidies - Klinefelter syndrome 47 XXY
1 in 1000 M births
NOT RARE
Sterility, development of breasts, high pitched voice
Clinical cytogenetics - can detect what
chromosomal aberrations
Clinical cytogenetics - indicated under what circumstances
Problems of early growth/development Stillbirth/neonatal death Fertility problems Pregnancy with advanced maternal age Also sometimes CA, family hx
Inheritance of a chromosomal defect -
Usually dominant, new mutations
Multiple abnormalities in affected children - often with developmental delay
Spontaneous abortions/multiple miscarriages
Infertility
Pedigree of a chromosomal defect - how can a person pass on a chromosomal aberration without being sick
Balanced alteration will perform a normal life but they will run into issues when they reproduce
Karyotype of a cancer cell line
3 or 4 or more copies of a certain chromosome because these do not stop dividing even if a genome goes wrong
Epigenetics is the study of
Heritable changes that do not involve changes in DNA sequence
Epigenetics - how do they work
Changes silence or activate chromosomal regions by DNA methylation/demethylation OR Histone acetylation/deacetylation
Epigenetics influences
Tee expression without changing the genomic sequence
Epigenetics - DNA methylation - methylation of DNA occurs where
On cytosine residues in CpG repeats
Epigenetics - DNA methylation - CpG repeats are found in
CpG islands - non methylated
Repetitive DNA - methylated
Epigenetics - DNA methylation - about 70% of the CpGs are
methylated (silenced)
Epigenetics - Histone acetylation - Acetylation of histones occurs wher
on the tail region
Epigenetics - Histone acetylation - acetylation of the histone changes what
the charge of the histone
Acetyl group = neg charge
Histones = need to be pos charged
Epigenetics - Histone acetylation - acetylation of histones does what
decreased the affinity to DNA
so it makes it stick less well to the DNA
And you are facilitating transcription of that region
Epigenetics - Histone acetylation - Deacetylated histones bind
more tightly to DNA
Epigenetics - Histone acetylation - Histone deacetylation
silences chromosomal regions
Increases their binding affinity and silences transcription
Epigenetics - Histone acetylation - In addition to acetylation, there are other histone modifications - what are they
Methylation
Phosphorylation
Ubiquitination
These modifications might constitute a “histone” code imposed on the DNA
Imprinting - what is it
Imprinting silences chromosomal regions by DNA methylation and histone deacetylation
Imprinting - reversible or stable?
Can be reversed but in general is stable through somatic cell division
Imprinting occurs -
During gemetogenesis to mark the paternal origin of chromosome
During development to permanently change the gene expression pattern of a cell line
Imprinting - is also the mechanism by which
X chromosome inactivation occurs
X chromosome inactivation - mediated by
Transcripts of the XIST gene
X chromosome inactivation - DNA is ____ and histones ____
DNA is methylated
Histones deacetylated
Imprinting related diseases - imprinting does what
silences a maternal or parental allele
If imprinting is incorrect, what happens
Gene dosage problems may arise where you have too much or too little genes in a cell
Imprinting occurs when
during development
Imprinting - explains what
Parent of origin effect of some mutations
Detrimental effects of uniparental disomy
What are two examples of parent of origin effects and issues with imprinting
Prader willi syndrome
Angelman Syndrome
Beckwith Wiedemann Syndrome
Prader Willi Syndrome - Caused by
Deletion on paternal copy of Ch 15 or maternal uniparental disomy
Prader Willi Syndrome - Rare or Common
Rare
Prader Willi Syndrome - s/s
Excessive food seeking bx
Hypogonadism
Mental retardation
Small hands, feet, facial features, hypotonia,
Angelman syndrome - caused by
Deletion on maternal copy of Ch 15 or paternal uniparental disomy
Angelman Syndrome - rare or common
Rare
Angelman syndrome - characterized by what
Unusual facial features (large mandible, open mouth)
Excessive laughter
Seizures, mvmnt and gait disorder
Severe mental retardation, absence of speech
Beckwith Wiedemann Syndrome - can be caused by what
Parternal uniparental disomy
Beckwith Wiedemann Syndrome - rare or common
Rare
Beckwith Wiedemann Syndrome - Characterized by
Micocephaly, macroglossia, umbilical hernia
Overabundance of growth factor 2 - multiple organ problems
Susceptible to CA
DNA silencing and CA
DNA silencing is important for preventing continuous cell division (CA)
DNA silencing and CA - Global hypomethylation
of DNA outside of CpG islands is found in most cancers
DNA silencing and CA - hypomethylation of DNA causes
Genetic instability:
- elevated activity of mobile genetic elements
- chromosomal abnormalities
DNA silencing and CA - hypomethylation of DNA causes genetic instability which causes
Cancer
Cancer causes genomic instability too
DNA silencing and CA - Hypermethylation of CpG islands in promoter
can shut down tumow suppressor geners
Effect of silencing equals effect of null mutation
DNA silencing and CA - Hypermethylation - rare or common
Probably rather common 10-15% of non familial breast CA due to hypermethylation of BRCA1 (not mutation)
