ZS 7: overerving Flashcards
Bespreek X-chromosoom inactivatie
- in een vrouw , zal in elke somatische cel cel (niet in haar gameten) , één x-chromosoom random geinactiveerd worden. Het geinactiveerd x-chromosoom is het Barr lichaampje. Deze is sterk gecondenseerd en onleesbaar (= constitueel hemizygoot).
- opgelet: soms zullen genen in het barr lichaampje niet geinactiveerd worden, ook in pseudoautosomale regios.
- Daarom zal een vrouw die heterozygoot is voor een ziekt op het x-chromosoom , mosaicisme vertonen.
- Soms kan er ook non-random inactivatie van een x-chromosoom kan plaatsvinden, afhankelijk van welke x-chromosoom het voordeligst is.
Bespreek mosaicisme
-vrouwen hebben een barlichaampje in elke cel ,van één van de 2 x-chromosomen.
-Post-zygotic mutations may result in somatic mosaicism that will have consequences only for that individual , But certain post-zygotic
mutations, often occurring comparatively early in development, may also
result in germ-line mosaicism
A person who has a substantial proportion
of mutant germ-line cells (a germ-line mosaic or gonadal mosaic)
may not show any symptoms but will produce some normal gametes and
some mutant gametes. The risks of having a subsequently affected child
are much higher than if an affected child carries a mutation that originated
in a meiotic division.
Bespreek pseudoautosomale regios
the X and Y have
some short gene-containing regions in common
autosomal inheritance !
the pseudoautosomal
regions that are located just before the telomere-associated
repeats at the ends of both the short and long chromosome arms
The pseudoautosomal regions are the
only regions of the X and Y that can pair up during male meiosis and
undergo recombination just like paired sequences do on homologous
autosomal chromosomes
at each meiosis, there is an obligate X–Y
crossover in the major pseudoautosomal region;
recombination is less
frequent in the minor pseudoautosomal region).
- de minor pseudoautosomale regio is gelegen op de grote arm, nabij de telomeer regio, in de X en y-chromosoom
de major pseudoautosomale regio op de kleine arm ,nabij de telomeer regio in de X en y-chromosoom
The X-specific region can engage in recombination
in female meiosis, and sequences in this region can be transmitted to
males or females; the Y-specific region is never involved in recombination
and so is also called the male-specific region.
(The large central regions of the X and Y do
not engage in recombination and are X-specific or
Y-specific (also a male-specific region because it is
not normally transmitted to females).)
welke weefsels worden het meest aangetast bij een mitochondriale DNA afwijking
weefsels die een hoge energiebehoeft hebben, zullen het meest leiden = spieren en hersenen
Bespreek heteroplasmy
Heteroplasmy is the presence of more than one type of organellar genome (mitochondrial DNA or plastid DNA) within a cell or individual. It is an important factor in considering the severity of mitochondrial diseases.
- het tegenovergestelda van homoplasmie waar dat alle mtDNA een mutatie draagt
- de hoeveelheid mtDNA in heteroplastische mitochondrion bepaalt de kracht van het ziekte
- een bottleneck ,waarbij sommige cellen minder van mutante mtDNA dragen dan andere, kan ervoor zorgen dat nakomelingen van een zieke moeder minder aangetast zijn
Although a human egg cell is haploid for nuclear DNA, it contains more
than 100,000 mtDNA molecules. A heteroplasmic mother can give rise
to children who differ widely from her and from each other in the ratio
of mutant to normal mtDNA molecules in their tissues (variable heteroplasmy).
As a result, there can be very significant clinical variability
between affected members of the same family.
Unlike in the nucleus,
where replication of a chromosomal DNA molecule
normally produces two copies, mitochondrial
DNA (mtDNA) replication is stochastic. When a
mitochondrion increases in mass in preparation for
cell division, the overall amount of mitochondrial
DNA increases in proportion, but individual mtDNAs
replicate unequally. In this example, the mtDNA
with the green tag fails to replicate and the one
with the red tag replicates to give three copies.
Variants of mtDNA can arise through mutation so
that a person can inherit a mixed population of
mtDNAs (heteroplasmy). Unequal replication of
pathogenic and nonpathogenic mtDNA variants
can have important consequences, as described
in Chapter 5.
Bespreek post-zygotische (somatische en germ-line mosaicisme) mutaties
Mutations can occur during gametogenesis and produce
sperm and eggs with a new mutant allele.
In addition, de novo pathogenic
mutations can also occur at any time in post-zygotic life. As a result of
post-zygotic mutations, each individual person is a genetic mosaic with
genetically distinct populations of cells that have different mutational
spectra.
Post-zygotic mutations may result in somatic mosaicism that will have
consequences only for that individual , But certain post-zygotic
mutations, often occurring comparatively early in development, may also
result in germ-line mosaicism
Bespreek locust heterogeniteit
The same clinical phenotype can often be produced by mutations in genes
at two or more loci.
The different genes often make related products that
work together as a complex or in a common pathway
Locus heterogeneity explains how parents who are both affected with the
same common recessive disorder produce multiple unaffected children.(vb dove ouders door recessieve afwijking die horende kinderen krijgen),
bespreek non-penetrantie
The penetrance of a single-gene disorder is the probability that a person
who has a mutant allele will express the disease phenotype.
Dominantly inherited disorders, by definition, are manifested in heterozygotes and
might be expected to show 100% penetrance. That might be true for certain
dominant disorders. For many others, however, penetrance is more
variable and the disorder can sometimes appear to skip a generation so
that a person who must have inherited the disease allele is unaffected
(non-penetrance—Figure 5.12).
Non-penetrance should not be viewed as surprising. Even in single-gene
disorders—in which, by definition, the phenotype is largely dictated by
the genotype at just one locus—
>other genes can play a part,
>as can epigenetic
>and environmental factors.
Bespreek Late onset afwijkingen
over time, for example. If pathogenesis involves a gradual process of cell death, it may take some time before the number of surviving cells drops to critically low levels that produce clinical symptoms.
In hereditary cancers, a mutation is inherited at a tumor-suppressing gene locus and a second, somatic mutation is required to initiate tumor formation.
The second mutation occurs randomly, but the probability of a second mutation increases with time and therefore with age.
Huntington disease is a classic example of a late-onset
single-gene disorder.
bespreek imprinting
Certain phenotypes show autosomal dominant inheritance with parentof-
origin effects
The parent-of-origin effects are due to an epigenetic mechanism known
as imprinting,
Genomic imprinting is an epigenetic phenomenon that causes genes to be expressed in a parent-of-origin-specific manner. Genes however, can also be partially imprinted.
Bespreek het verschil tussen late-onset afwijkingen , en awijkingen die anticipatie vertonen
late-onset: in 1 persoon, op een later leeftijd manifestatie
Anticipatie : in 1 familie, zwaarder en zwaarder wordende ziekteverschijnsel op nakomelingen
Purifying (negative) selection
Purifying (negative) selection. If a person affected by genetic
disease is not likely to reproduce, disease alleles are lost from the population.
This effect is much more pronounced in early-onset dominant
conditions, in which—with the exception of non-penetrance—anyone
with a mutant allele is affected by the time of puberty.
bespreek genetic drift
wanneer er in een kleine populatie, slechts bepaalde groepen van mensen met specifieke allelen zich voortplanten, zullen die allelen prominent aanwezig zijn in de populatie. Zo zijn er dus grote allelfrequentie veranderingen tussen generaties.
In een grote populatie heeft dit weinig effect
The bottleneck effect is an extreme example of genetic drift that happens when the size of a population is severely reduced. Events like natural disasters (earthquakes, floods, fires) can decimate a population, killing most indviduals and leaving behind a small, random assortment of survivors.
bespreek heterozygote voordeel en balancing selection
vb: sikkelcel anemie
sometimes a disadvantageous
allele can also simultaneously be an advantageous allele. A form of natural
selection called balancing selection can cause a harmful disease
allele to increase in frequency in a population because carriers of the
mutant allele have a higher fitness than normal individuals (heterozygote
advantage).
bespreek natuurlijke selectie
Recall that natural selection works to eliminate disadvantageous alleles
within the population (purifying selection = negatieve selectie) and also to promote an
increase in frequency of advantageous alleles (positive selection).
That
occurs because natural selection works though the genetic fitness of individuals
(their ability to reproduce and have children who survive to a
reproductive age):
