Case 13 SBA 4

Question 1

Mosaicism

Answer 1

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.

Question 2

Mosaicism mechanism of action

Answer 2

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.

Question 3

Mosaicism- when you get the mutation

Answer 3

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.

Question 4

What can Mosaicism affect?

Answer 4

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

Question 5

Difference between Mosaicism and chimerism

Answer 5

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.

Question 6

The two mechanisms of Chimerism

Answer 6

• 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

Question 7

Severity of Mosaicism

Answer 7

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

Question 8

Mosaicism and non-disjunction

Answer 8

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.

Question 9

Monosomy 21 vs Trisomy 21

Answer 9

• Monosomy 21 causes cell senescence

* Trisomy 21 does not inhibit mitosis

Question 10

Severe Trisomy 21 mosaicism

Answer 10

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.

Question 11

Mild Trisomy 21 mosaicism

Answer 11

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.

Question 12

Mechanism of DNA mutation mosaicism

Answer 12

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.

Question 13

Germline mosaicism

Answer 13

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.

Question 14

Somatic mosaicism

Answer 14

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

Question 15

Mosaic fragile X syndrome

Answer 15

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.

Question 16

Mosaic downs syndrome

Answer 16

Rare often causes less severe forms of Down’s syndrome

Question 17

Mosaic Turners syndrome

Answer 17

Full or partial absence of X chromosomes in only some cells

Question 18

Genomic imprinting

Answer 18

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.

Question 19

Methylated

Answer 19

Gene turned off

Question 20

Acetylated

Answer 20

Gene turned on

Question 21

How are genes turned on or off

Answer 21

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.

Question 22

Where are methyl groups added

Answer 22

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

Question 23

Gender specific genomic imprints

Answer 23

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.

Question 24

How are gender specific genomic imprints inherited

Answer 24

The embryo has gender specific germ line cells and somatic cells with both a maternal and paternal imprint.

Question 25

Germline programming

Answer 25

• Male or female imprints are erased from the germ cells.

* Gender specific maternal and paternal imprints are applied in mature germline cells.

Question 26

The roles imprinted genes play during embryogenesis

Answer 26

• Growth- growth regulators.
• Brain- spatial learning, socialisation, aggression, memory, learning, motor function.
• Placenta- growth, nutrient transfer.

Question 27

Prader-willi syndrome

Answer 27

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.

Question 28

Angelman syndrome

Answer 28

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.

Question 29

Zygote

Answer 29

A diploid cell resulting from the fusion of two haploid gametes (an egg and a sperm)

Question 30

Somatic

Answer 30

Relating to the body i.e. body cells

Question 31

Germline/gonadal

Answer 31

Relating to cells that pass on their genetic material to progeny

Question 32

Gamete

Answer 32

Mature haploid sex cell (egg or sperm)

Question 33

Genotype

Answer 33

Genetic makeup of an organism

Question 34

Phenotype

Answer 34

Observable characteristics resulting from an individuals genes and environment

Question 35

Twinning

Answer 35

Two offspring resulting from a single pregnancy

Question 36

Monozygotic twins

Answer 36

1/300 births in the UK, they are identical

Question 37

Dizygotic twins

Answer 37

1/100 births in the UK, non-identical

Question 38

Variance in frequency of twins

Answer 38

Monozygotic twinning is fairly fixed but Dizygotic twinning its less common in Asia and more common in Nigeria (1/22).

Question 39

Monozygotic twins 2 cell stage

Answer 39

The pre-embryo splits and forms two conceptus which each develop separately with their own placenta and amniotic sac.

Question 40

Monozygotic twin formation

Answer 40

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.

Question 41

Monozygotic twins 4-8 days

Answer 41

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.

Question 42

Monozygotic twins 8-12 days

Answer 42

Separates post implantation when the inner cell mass splits. They have a common placenta and amniotic sac

Question 43

Monozygotic twins after 13 days

Answer 43

You get conjoined twins which can result when the inner cell mass does not completely separate. The cells only partially separate.

Question 44

Formation of Dizygotic twins

Answer 44

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.

Question 45

Risk factors for Dizygotic twins

Answer 45

Maternal age, family history and fertility treatment

Question 46

How can you tell if a disease is Sex (X) linked?

Answer 46

• 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

Question 47

How can you tell if a disease is autosomal dominant

Answer 47

• 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.

Question 48

How can you tell if a disease is autosomal recessive?

Answer 48

• 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