MOSAICISM and CHIMERISM

Question 1

mosaicism

Answer 1

a condition in which tissues of genetically different types occur in the same organism but all the cells have arisen from a single zygote

Question 2

mosaicism refers to the

Answer 2

presence of two or more populations of cells with different genotypes in one individual who has developed from a single fertilized egg

Question 3

mosaicism is caused when

Answer 3

a mitotic mutation arises early in development, the resulting individual will be a mixture of cells some with the mutation and some without mutation

Question 4

examples of mosaicism

Answer 4

1. pigmentary mosaicism

2. segmental/mosaic neurofibromatosis(MNF1)

Question 5

diagnosing mosaicism

Answer 5

A. Cytogenetic analysis on bloodcan detect mosaicism –a percentage of cells will show the abnormal karyotype while the rest of the cells will show a normal karyotype

•Sometimes more difficult –may need to look at different tissues (e.g. skin as well as blood)

Question 6

mechanisms for trisomic mosaicism

Answer 6

• The most common form of mosaicism found through prenatal diagnosis and in neonates involves trisomies
• The individual now carries two cell lines, one trisomic and one normal

.•Two mechanisms are described:

Question 7

mechanism 1- non-disjunction in early normal embryo

Answer 7

–a nondisjunction event during an early cell division in a normal embryo leads to a fraction of the cells with a trisomy

Question 8

mechanism 2- trisomic rescue

Answer 8

•A trisomicembryo undergoes nondisjunction and some of the cells in the embryo revert to the normal chromosomal arrangement (this is called ‘trisomicrescue’)

Question 9

mosaic down syndrome

Answer 9

1. 46,XX/47,XX,+21

2. MOSAICISM LEADS TO A MILDER PHENOTYPE THAN IN NON-MOSAIC PATIENTS WITH the same disorder

Question 10

a milder mosaic phenotype

Answer 10

mosaic 22q11 microdeletion syndrome

Question 11

trisomy 14/9 mosaic

Answer 11

Although complete trisomy14 or 9 is not compatible with postnatal life, trisomymosaicismfor these chromosomes has been diagnosed in newborns with multiple congenital anomalies.

Question 12

sex chromosome mosaicism

Answer 12

• Turner Syndrome (45,X0)–Usually infertile
• Turner Syndrome mosaics (45,XO/46,XX)–About 30%of Turner’s females are mosaics–Often multiple miscarriages (>3)
• Approx 7% spontaneous abortions are XO conceptuses–Some individuals, possible to conceive naturally

Question 13

cytogenetic nomenclature = 47,XY,+13[9]/ 46,XY[27]

Answer 13

47 chromosomes
male
addition of chromosome
trisomic chromosome 13
9+ 27 analyzed cells and 9  are abnormal
2 cell lines

Question 14

X chromosome inactivation

Answer 14

two cell lines

• Female mammals–One X is inactivated in all cells
• Which X to inactivate is initially a completely random process
• In this way, all-female mammals are genetic mosaics

Question 15

two cells of mosaicism are

Answer 15

1. somatic mosaicism

2. germline mosaicism

Question 16

somatic mosaicism

Answer 16

1. normal and abnormal cell lines within the cells of the body, may include or may not include germline
2. mutation cannot be transmitted to the offspring unless present in the germline

Question 17

germline mosaicism

Answer 17

1. formerly gonadal mosaicism
2. mutation confined to a portion of germ cells(ova/sperm)
3. mutation can be transmitted to the offspring

Question 18

germline mosaicism p2

Answer 18

•Most individuals are unaware they possess a germline mutation until they have children that are affected.

–Because the mosaic germline mutation is present in the egg or sperm cell, it will also be present in all cells of the child developing from that germ cell.

•If it is an autosomal dominant mutation, the child will be affected with the disorder, and will not be a mosaic-like his or her parent. They will have a 50% chance of passing it on to any offspring.

Question 19

germline vs somatic mosaicism

Answer 19

• Recurrence risk is important to consider!
• Germlinemosaicismis typically seen in autosomal dominantorX-linked disorders

–evident or suspected when an unaffected parent has two or more children with the same pathogenic variant/chromosome anomaly

–Molecular genetic testing using blood or tissue samples (other than germline tissue) from an individual with germline mosaicism will not identify the pathogenic variant

–The recurrence risk for a genetic condition is proportionate to the number of gamete cells that contain the pathogenic variant or chromosome anomaly.

–Germlinemosaicismhas have been reported in numerous genetic conditions; some genetic conditions are associated with a higher risk for germline mosaicism(e.g., Duchenne muscular dystrophy, osteogenesis imperfecta)•

Question 20

chimerism

Answer 20

an organism carrying cell populations derived from two or more different zygotes of the same or different species

Question 21

non-identical twins

Answer 21

• By definition, transplant and transfusion patients are also chimeras
• Non-identical twins may be chimeras

–Twin embryos often share a blood supply in the placenta, allowing blood stem cells to pass from one and settle in the bone marrow of the other

–About 8% of non-identical twin pairs are chimeras