Case 13 SBA 4 Flashcards
Mosaicism
The presence of two or more cell lines in one individual, different cells will have a different set of genetics. However, all cells originate from a single zygote, one egg and one sperm cell.
Mosaicism mechanism of action
During the first couple mitotic divisions a mutation arises in one cell, all subsequent cells from that original cell will have this mutation. Whereas the others won’t. As an adult some cells will have the genetics with this mutation and some cells will not. For example, calico cats.
Mosaicism- when you get the mutation
The error occurs during mitosis post fertilisation. It can happen at any stage after fertilisation, the further after fertilisation it occurs the less tissue which will carry this mutation. If it happens earlier the mutated cell will give rise to a higher percentage of overall tissue.
What can Mosaicism affect?
Can affect the whole individual or a specific tissue. Can occur in somatic or germline cells. The Germline mutations will affect the offspring but not the parent. For example, an inherited disease may randomly emerge
Difference between Mosaicism and chimerism
Mosaicism occurs due to a mutation in a cell of a single zygote. In chimerism one individual has two genetically distinct cell lines derived from two or more zygotes.
The two mechanisms of Chimerism
- Two eggs are fertilised by two separate sperm cells simultaneously but the two zygotes fuse producing one embryo
- An exchange of cells between non-identical twins via the placenta
Severity of Mosaicism
If a mutation happens at the second mitotic division, ¼ of the cells will be mutated. If it happened at the third mitotic division 1/8th of the cells would be affected etc
Mosaicism and non-disjunction
Must be after the first mitotic division. If it happened too early the embryo would miscarry as the monosomy (cells lacking a chromosome) would die. If it happened later there would be enough left over cells to cover the loss.
Monosomy 21 vs Trisomy 21
- Monosomy 21 causes cell senescence
* Trisomy 21 does not inhibit mitosis
Severe Trisomy 21 mosaicism
Failure at the second mitotic division where the chromosomes do not effectively split, 3 copies of chromosome 21 go to one cell and 1 go to the other. 25% of cells will have 3 copies of chromosome 21 and 25% of the cells don’t develop as monosomic cells are lethal, 50% of cells will be normal. This results in a third of the body being Trisomy 21.
Mild Trisomy 21 mosaicism
Mitotic non-disjunction happens at the 4th division. Means 1/15 cells have the Trisomy 21. 1/16 cells will have Monosomy 21 but these will die off. Because less of the cells are affected they have a mild form of Down’s syndrome with more mild symptoms.
Mechanism of DNA mutation mosaicism
Proteus syndrome, a base mutation occurs in a cell. Any cells which originate from this cell will carry this mutation. If it occurs earlier (2nd division) it will be a non-tissue specific mosaicism and contribute to multiple tissue. If the mutation occurs later it will be a tissue specific mosaicism which only affects one tissue. Depending on the mutation it could causes a phenotypic change or disease.
Germline mosaicism
Mosaicism in egg or sperm cell. Individual is typically not affected by the disorder. Can be passed to offspring. Most commonly seen with autosomal dominant or X-linked disease.
Somatic mosaicism
Mosaicism in body cells. Individual may or may not be affected by the disorder. Phenotype depends on number and type of cells affected. Depending on when the mutation occurs during development is can be present in both somatic or germline cells
Mosaic fragile X syndrome
Fragile X can also be caused by a gene deletion. It causes Mosaic cases of males with a mix of normal X and X gene deletions. Because it’s a different mechanism and affects less cells it may not have a classic fragile X phenotype and less cells will be affects.
Mosaic downs syndrome
Rare often causes less severe forms of Down’s syndrome
Mosaic Turners syndrome
Full or partial absence of X chromosomes in only some cells
Genomic imprinting
Both parents contribute to the genetic material of their offspring but not all genes from your parents are expressed equally. Some genes are solely expressed from either the maternal or paternal chromosome. One gene in a gene pair can be switched off. Only 100 genes are expressed exclusively in this way. This is known as genomic imprinting (only get gene product from one chromosome.
Methylated
Gene turned off
Acetylated
Gene turned on
How are genes turned on or off
Genomic imprinting is controlled by epigenetics. It changes genes that are not carried in the DNA code itself. It can either switch on or off gene expression. Its main mechanism is DNA methylation, where methyl groups are added to the cytosine base of the DNA in order to silence the genes.
Where are methyl groups added
The CpG region is around the promoter region of the gene and contains repeated units of C and G. The methyl groups bind to these CpG islands to turn off gene expression as it stops transcription factors from binding
Gender specific genomic imprints
Adults somatic cells maintain the maternal and paternal imprints that they inherited from their mother and father. In germline cells you have gender specific imprints, in sperm cells you just have the paternal imprint pattern.
How are gender specific genomic imprints inherited
The embryo has gender specific germ line cells and somatic cells with both a maternal and paternal imprint.
Germline programming
- Male or female imprints are erased from the germ cells.
* Gender specific maternal and paternal imprints are applied in mature germline cells.
The roles imprinted genes play during embryogenesis
- Growth- growth regulators.
- Brain- spatial learning, socialisation, aggression, memory, learning, motor function.
- Placenta- growth, nutrient transfer.
Prader-willi syndrome
Learning disability. There is a DNA mutation or loss of paternal chromosome 15, because the maternal copy has been switched off you have no back up copy. So, the gene’s products will not be produced. It is the SNRP gene which is important for regulating RNA.
Angelman syndrome
Symptoms are learning disabilities, seizures and smiling and laughing a lot. Due to a mutation in the UBE3A gene on the maternal chromosome 15. As the paternal copy is methylated you do not have a back up. The gene is important in regulating protein degradation. You lose function in the gene.
Zygote
A diploid cell resulting from the fusion of two haploid gametes (an egg and a sperm)
Somatic
Relating to the body i.e. body cells
Germline/gonadal
Relating to cells that pass on their genetic material to progeny
Gamete
Mature haploid sex cell (egg or sperm)
Genotype
Genetic makeup of an organism
Phenotype
Observable characteristics resulting from an individuals genes and environment
Twinning
Two offspring resulting from a single pregnancy
Monozygotic twins
1/300 births in the UK, they are identical
Dizygotic twins
1/100 births in the UK, non-identical
Variance in frequency of twins
Monozygotic twinning is fairly fixed but Dizygotic twinning its less common in Asia and more common in Nigeria (1/22).
Monozygotic twins 2 cell stage
The pre-embryo splits and forms two conceptus which each develop separately with their own placenta and amniotic sac.
Monozygotic twin formation
Monozygotic twins originate from a single egg and a single sperm. They are genetically identical. When the zygote is dividing the cell mass splits into two to form two zygotes.
Monozygotic twins 4-8 days
The pre-implantation inner cell mass splits, they have a common placenta but separate amniotic sacs. The cell has already began to develop trophoblasts and blastocyts.
Monozygotic twins 8-12 days
Separates post implantation when the inner cell mass splits. They have a common placenta and amniotic sac
Monozygotic twins after 13 days
You get conjoined twins which can result when the inner cell mass does not completely separate. The cells only partially separate.
Formation of Dizygotic twins
Dizygotic twins are two separate eggs fertilised by two separate sperm cells. They are siblings which share 50% of their genes, they can be the same or different gender. Each embryo implants separately so they have separate placentas and amniotic sacs.
Risk factors for Dizygotic twins
Maternal age, family history and fertility treatment
How can you tell if a disease is Sex (X) linked?
- Only men affected.
- Passed from mother to son.
- Only present in branches where mother is a carrier
- Only affects females, when a female carrier and a male with the disease have children
How can you tell if a disease is autosomal dominant
- Affects both males and females.
- No carriers, you either have the disease or not.
- Children get the disease even when only one of the parents has the disease. The child has at least one non disease allele but is still displaying the disease so it must be dominant.
- Affects more individuals then would be predicted with a recessive allele.
How can you tell if a disease is autosomal recessive?
- Affects both males and females.
- Can only be present if 2 carriers or a carrier and someone with the disease has children.
- Not present in the branch which does not have a disease allele.
- Affects less individuals then would be predicted with a dominant allele
