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==Genetic Abnormality Topics==
==Genetic Abnormality Topics==
These statistics do not directly relate to trisomy mosaicism frequency, but that of genetic risk related to maternal age for all abnormalities.
===Genetic Risk Maternal Age===
===Genetic Risk Maternal Age===
{{Genetic risk maternal age table}}
{{Genetic risk maternal age table}}

Revision as of 14:56, 19 March 2019

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Introduction

Chromosomes in trisomy 21

This page gives a general introduction to information about the genetic abnormality of trisomy mosaicism. The term "trisomy" refers to the abnormal copy number of a specific chromosome in all cells, that is 3 copies instead of 2. The abnormality is identified by the chromosome that is present as 3 copies within the cell. In humans, the most common trisomy is Trisomy 21 or Down syndrome. Other identified human trisomies include Trisomy 13, Trisomy 18 and Trisomy X.

In contrast, a "mosaicism" is a rare chromosome disorder characterized by having an extra copy of a chromosome in a proportion, but not all, of a person’s cells. These are examples of a class of very rare and not inherited genetic disorders.


Genetic Links: genetic abnormalities | maternal age | Trisomy 21 | Trisomy 18 | Trisomy 13 | Trisomy X | trisomy mosaicism | Monosomy | Fragile X | Williams | Alagille | Philadelphia chromosome | mitochondria | VACTERL | hydatidiform mole | epigenetics | Prenatal Diagnosis | Neonatal Diagnosis | meiosis | mitosis | International Classification of Diseases | genetics


Abnormality Links: abnormal development | abnormal genetic | abnormal environmental | Unknown | teratogens | ectopic pregnancy | cardiovascular abnormalities | coelom abnormalities | endocrine abnormalities | gastrointestinal abnormalities | genital abnormalities | head abnormalities | integumentary abnormalities | musculoskeletal abnormalities | limb abnormalities | neural abnormalities | neural crest abnormalities | placenta abnormalities | renal abnormalities | respiratory abnormalities | hearing abnormalities | vision abnormalities | twinning | Developmental Origins of Health and Disease |  ICD-11
Historic Embryology  
1915 Congenital Cardiac Disease | 1917 Frequency of Anomalies in Human Embryos | 1920 Hydatiform Degeneration Tubal Pregnancy | 1921 Anencephalic Embryo | 1921 Rat and Man | 1966 Congenital Malformations

Some Recent Findings

Human idiogram
  • The BabySeq Project "The BabySeq Project is a first-of-its-kind randomized clinical trial designed to examine how best to use genomics in clinical pediatric medicine by creating and safely testing methods for integrating sequencing into the care of newborns." Clinical Trials


More recent papers  
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Search term: Trisomy Mosaicism

Older papers  
These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.

See also the Discussion Page for other references listed by year and References on this current page.

Trisomy 22 Mosaicism

Rare Disease Database - The characteristic features of mosaic trisomy 22 typically include prenatal and postnatal growth failure or delay, asymmetrical development of the two sides of the body (hemidystrophy), congenital heart defects. While some patients with mosaic trisomy 22 have abnormal cognitive development, normal development has been documented for some children."

Trisomy 18 Mosaicism

[1] - "Blood lymphocyte and skin fibroblast karyotypes were normal. He died in the neonatal period of postoperative complications. On interphase fluorescence in-situ hybridization (FISH) using autopsy specimens, a significant number of cells in the liver (17%) were trisomic for chromosome 18, compared to normal control liver tissue. However, interphase FISH analyses of blood lymphocytes, skin fibroblasts, and kidney tissue were normal."

Trisomy 17 Mosaicism

NIH - rare diseases - "Some cases of trisomy 17 mosaicism detected during pregnancy have been confirmed in the baby after birth. The symptoms reported include: developmental delays, body asymmetry, slow growth, and cerebellar hypoplasia. Again, signs and symptoms may vary in these individuals depending on which cells and how many cells contain an extra chromosome 17."

Trisomy 14 Mosaicism

Rare Disease Database - "The disorder may be characterized by growth delays before birth (intrauterine growth retardation); failure to grow and gain weight at the expected rate (failure to thrive) during infancy; delays in the acquisition of skills requiring the coordination of mental and physical abilities (psychomotor delays); and mental retardation. Affected infants also have distinctive abnormalities of the head and facial (craniofacial) region, such as a prominent forehead; deeply set, widely spaced eyes; a broad nasal bridge; and low-set, malformed ears. Additional craniofacial abnormalities may include an unusually small lower jaw (micrognathia); a large mouth and thick lips; and incomplete closure or abnormally high arching of the roof of the mouth (palate). Many affected infants also have structural malformations of the heart (e.g., tetralogy of Fallot). In some cases, additional physical abnormalities may also be present."

Trisomy 12 Mosaicism

[2] - "meiotic origin of the trisomy, maternal meiosis I, was determined. Mosaic aneuploidy was suspected because of pigmentary dysplasia, a frequent but non-specific finding in chromosomal mosaicism. The severe phenotype of this child, who died in infancy with a complex heart malformation, was probably a result of the high percentage of trisomic cells. Cytogenetic and interphase fluorescent in situ hybridization analyses showed a highly variable distribution of aneuploid cells in the nine tissues studied, from none in blood and ovary to 100% in spleen and liver."

Trisomy 9 Mosaicism

Rare Disease Database - "Associated symptoms and findings may vary greatly in range and severity, depending on the percentage of cells with the extra chromosome. However, common features include growth deficiency before birth (intrauterine growth restriction or IUGR); structural malformations of the heart that are present at birth (congenital heart defects); and/or distinctive differences in the shape of the skull and facial (craniofacial) region, such as a sloping forehead, a bulbous nose, short eyelid folds (palpebral fissures), deeply set eyes, and/or low-set ears. The syndrome may also be characterized by musculoskeletal, genital, kidney (renal), and/or additional physical anomalies. Intellectual disability is common and varies in severity."

Trisomy 8 Mosaicism

NIH - rare diseases - "The signs and symptoms vary, but may include distinctive facial features; intellectual disability; and joint, kidney, cardiac, and skeletal abnormalities. Males are more frequently affected than females."

Trisomy 2 Mosaicism

[3] NIH - rare diseases - "Features of trisomy 2 mosaicism may include intrauterine growth restriction (IUGR), any of various birth defects, distinctive facial features, growth delay, developmental delays, and intellectual disabilities.[1][2] However, children with trisomy 2 mosaicism with no significant medical problems have been reported (although long-term follow-up was not available)."


Genetic Abnormality Topics

These statistics do not directly relate to trisomy mosaicism frequency, but that of genetic risk related to maternal age for all abnormalities.

Genetic Risk Maternal Age

Genetic Risk Maternal Age
Age of Mother
Risk of Trisomy 21
Risk of Any Chromosomal Abnormality
20
1 in 1667
1 in 526
21
1 in 1667
1 in 526
22
1 in 1429
1 in 500
23
1 in 1429
1 in 500
24
1 in 1250
1 in 476
25
1 in 1250
1 in 476
26
1 in 1176
1 in 476
27
1 in 1111
1 in 455
28
1 in 1053
1 in 435
29
1 in 1000
1 in 417
30
1 in 952
1 in 384
31
1 in 909
1 in 384
32
1 in 769
1 in 323
33
1 in 625
1 in 286
34
1 in 500
1 in 238
35
1 in 385
1 in 192
36
1 in 294
1 in 156
37
1 in 227
1 in 127
38
1 in 175
1 in 102
39
1 in 137
1 in 83
40
1 in 106
1 in 66
41
1 in 82
1 in 53
42
1 in 64
1 in 42
43
1 in 50
1 in 33
44
1 in 38
1 in 26
45
1 in 30
1 in 21
46
1 in 23
1 in 16
47
1 in 18
1 in 13
48
1 in 14
1 in 10
49
1 in 11
1 in 8
Table Data[4][5][6]
Genetic Links: genetic abnormalities | maternal age | Trisomy 21 | Trisomy 18 | Trisomy 13 | Trisomy X | trisomy mosaicism | Monosomy | Fragile X | Williams | Alagille | Philadelphia chromosome | mitochondria | VACTERL | hydatidiform mole | epigenetics | Prenatal Diagnosis | Neonatal Diagnosis | meiosis | mitosis | International Classification of Diseases | genetics


References

  1. Shashi V, Golden WL, von Kap-Herr C & Wilson WG. (1996). Constellation of congenital abnormalities in an infant: a new syndrome or tissue-specific mosaicism for trisomy 18?. Am. J. Med. Genet. , 62, 38-41. PMID: 8779322 <38::AID-AJMG8>3.0.CO;2-S DOI.
  2. DeLozier-Blanchet CD, Roeder E, Denis-Arrue R, Blouin JL, Low J, Fisher J, Scharnhorst D & Curry CJ. (2000). Trisomy 12 mosaicism confirmed in multiple organs from a liveborn child. Am. J. Med. Genet. , 95, 444-9. PMID: 11146464
  3. Sifakis S, Velissariou V, Papadopoulou E, Petersen MB & Koumantakis E. (2004). Prenatal diagnosis of trisomy 2 mosaicism: a case report. Fetal. Diagn. Ther. , 19, 488-90. PMID: 15539872 DOI.
  4. Hook EB. (1981). Rates of chromosome abnormalities at different maternal ages. Obstet Gynecol , 58, 282-5. PMID: 6455611
  5. Hook EB, Cross PK & Schreinemachers DM. (1983). Chromosomal abnormality rates at amniocentesis and in live-born infants. JAMA , 249, 2034-8. PMID: 6220164
  6. Schreinemachers DM, Cross PK & Hook EB. (1982). Rates of trisomies 21, 18, 13 and other chromosome abnormalities in about 20 000 prenatal studies compared with estimated rates in live births. Hum. Genet. , 61, 318-24. PMID: 6891368

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Terms

  • anaphase - (Greek, ana = up, again) Cell division term referring to the fourth mitotic stage, where the paired chromatids now separate and migrate to spindle poles. This is followed by telophase.
Mitosis Phases: prophase - prometaphase - metaphase - anaphase - telophase
  • anaphase B - Cell division term referring to the part of anaphase during which the poles of the mitotic spindle move apart. (More? Cell Division - Mitosis)
  • aneuploidy - Genetic term used to describe an abnormal number of chromosomes mainly (90%) due to chromosome malsegregation mechanisms in maternal meiosis I.
  • disomy - Genetic term referring to the presence of two chromosomes of a homologous pair in a cell, as in diploid. See chromosomal number genetic disorders uniparental disomy and aneuploidy. Humans have pairs usually formed by one chromosome from each parent.
  • meiosis I (MI) The first part of meiosis resulting in separation of homologous chromosomes, in humans producing two haploid cells (N chromosomes, 23), a reductional division.
Meiosis I: Prophase I - Metaphase I - Anaphase I - Telophase I
  • meiosis II - (MII) The second part of meiosis. In male human spermatogenesis, producing of four haploid cells (23 chromosomes, 1N) from the two haploid cells (23 chromosomes, 1N), each of the chromosomes consisting of two sister chromatids produced in meiosis I. In female human oogenesis, only a single haploid cell (23 chromosomes, 1N) is produced.
Meiosis II: Prophase II - Metaphase II - Anaphase II - Telophase II
  • prometaphase - (Greek, pro = before) Cell division term referring to the second mitotic stage, when the nuclear envelope breaks down into vesicles. Microtubules then extend from the centrosomes at the spindle poles (ends) and reach the chromosomes. This is followed by metaphase.
  • Philadelphia chromosome - (Philadelphia translocation) Genetic term referring to a chromosomal abnormality resulting from a reciprocal translocation between chromosome 9 and 22 (t(9;22)(q34;q11)). This is associated with the disease chronic myelogenous leukemia (CML).
  • prophase - (Greek, pro = before) Cell division term referring to the first mitotic stage, when the diffusely stained chromatin resolves into discrete chromosomes, each consisting of two chromatids joined together at the centromere.
  • telophase - Cell division term referring to the fifth mitotic stage, where the vesicles of the nuclear envelope reform around the daughter cells, the nucleoli reappear and the chromosomes unfold to allow gene expression to begin. This phase overlaps with cytokinesis, the division of the cell cytoplasm.
  • trisomy mosaicism - a rare chromosome disorder characterized by having an extra copy of a chromosome in a proportion, but not all, of a person’s cells.
  • uniparental disomy - Genetic term referring to cells containing both copies of a homologous pair of chromosomes from one parent and none from the other parent.


Cell Division Terms (expand to view) 
meiosis | mitosis
  • anaphase - (Greek, ana = up, again) Mitosis term referring to the fourth stage, where the paired chromatids now separate and migrate to spindle poles. This is followed by telophase.
  • anaphase A - Mitosis term referring to the part of anaphase during which the chromosomes move.
  • anaphase B - Mitosis term referring to the part of anaphase during which the poles of the mitotic spindle move apart.
  • aneuploidy - (aneuploid) term used to describe an abnormal number of chromosomes mainly (90%) due to chromosome malsegregation mechanisms in maternal meiosis I.
  • aster - (Latin, aster = star) star-like object visible in most dividing eukaryotic cells contains the microtubule organizing center.
  • astral microtubule - spindle apparatus microtubule (MT) originating from the centrosome which does not connect to a kinetochore. These microtubules only exist during mitosis, the other spindle types are polar and kinetochore microtubules.
  • autosomal inheritance - term used in hereditary diseases which means that the disease is due to a DNA error in one of the 22 chromosome pairs that are not sex chromosomes. Both boys and girls can then inherit this error. If the error is in a sex chromosome, the inheritance is said to be sex-linked.
  • bivalent - (tetrad) a pair of homologous chromosomes physically held together by at least one DNA crossover.
  • bouquet stage - meiosis term for when in prophase transition to the zygotene stage, the chromosome telomeres attachment to the inner nuclear envelope and form a cluster. This occurs before the onset of homologous pairing and synapsis. The name comes from the chromosomes resembling a "bouquet of flowers".
  • diploid - (Greek, di = double + ploion = vessel) having two sets of chromosomes (2n), this is the normal euploidy state for all human cells, other than gametes that are haploid (n, a single set of chromosomes).
  • diplotene stage- (diplotene phase, diplonema; Greek, diplonema = "two threads") meiotic stage seen during prophase I, the chromosomes separate from one another a small amount giving this appearance. In the developing human ovary, oocytes remain at the diplotene stage from fetal life through postnatal childhood, until puberty when the lutenizing hormone (LH) surges stimulate the resumption of meiosis. Prophase I, is divided into 5 stages (leptotene, zygotene, pachytene, diplotene, diakinesis) based upon changes associated with the synaptonemal complex structure that forms between two pairs of homologous chromosomes.
  • euploidy - the normal genome chromosomal set (n, 2n, 3n) or complement for a species, in humans this is diploid (2n). The other classes of numerical chromosomal abnormalities include aneuploidy, polyploidy and mixoploidy.
  • FUCCI - Acronym for Fluorescence Ubiquitination Cell Cycle Indicator a molecular tool for identifying the stage in the cell cycle. In G0/G1 cells express a red fluorescent protein and S/G2/M cells express a green fluorescent protein. (More? Tooth Development Movie)
  • haploid - (Greek, haploos = single) Having a single set of chromosomes (n) as in mature germ/sex cells (oocyte, spermatozoa) following reductive cell division by meiosis. Normally cells are diploid, containing 2 sets of chromosomes. Ploidy refers to the number of sets of chromosomes in the nucleus of a cell.
  • heteroplasmy - presence of more than one type of organellar genome. In humans this can refer to variations in the mitochondrial DNA (mtDNA). (More? PMID 26281784)
  • homologous chromosomes - meiosis term for the two matching (maternal and one paternal) chromosomes that align during meiosis I.
  • homologous recombination - meiosis term when DNA of homologous chromosomes is covalently exchanged to produce chromosomes with new allele combinations, and also links homologous chromosomes with each other to form a bivalent
  • human genome - DNA within the 23 nucleus chromosome pairs and the cytoplasmic mitochondrial DNA.
  • kinetochore - the protein structure formed on chromatids where the spindle kinetochore microtubules attach during cell division.
  • kinetochore microtubule - spindle apparatus microtubule (MT) that attaches to the chromosome kinetochore by its plus end, the other spindle types are astral and polar microtubules.
  • kinesin - a microtubule (MT) motor protein that exists in many isoforms and most move towards the MT positive end. Different isoforms have different functions within the spindle apparatus. PMID 20109570
  • meiosis - reductive cell division required to produce germ cells (oocyte, spermatozoa) and for sexual reproduction. Note that only spermatozoa complete meiosis before fertilisation. Chromosome number is reduced from diploid to haploid, during this process maternal and paternal genetic material are exchanged. All other non-germ cells in the body divide by mitosis. (More? Meiosis | Spermatozoa Development | Oocyte Development | Week 1)
  • meiosis I - (MI) the first part of meiosis resulting in separation of homologous chromosomes, in humans producing two haploid cells (N chromosomes, 23), a reductional division.
  • meiosis II - (MII) the second part of meiosis. In male human spermatogenesis, producing of four haploid cells (23 chromosomes, 1N) from the two haploid cells (23 chromosomes, 1N), each of the chromosomes consisting of two sister chromatids produced in meiosis I. In female human oogenesis, only a single haploid cell (23 chromosomes, 1N) is produced. Meiosis II: Prophase II - Metaphase II - Anaphase II - Telophase II.
  • meiotic silencing of unsynapsed chromatin - (MSUC) an aneuploidy protective mechanism for subsequent generations, during meiosis where chromosomes are silenced that fail to pair with their homologous partners.
  • merotelic kinetochore - cell division abnormality in chromosomal attachment that occurs when a single kinetochore is attached to microtubules arising from both spindle poles. Normal chromosomal attachment in early mitosis, is by only one of the two sister kinetochores attached to spindle microtubules (monotelic attachment) later sister kinetochores attach to microtubules arising from opposite spindle poles (amphitelic attachment).
  • metaphase - mitosis term referring to the third stage where mitotic spindle kinetochore microtubules align chromosomes in one midpoint plane. Metaphase ends when sister kinetochores separate. Originally based on light microscopy of living cells and electron microscopy of fixed and stained cells. A light microscope analysis called a "metaphase spread" was originally used to detect chromosomal abnormalities in cells. Mitosis Phases: prophase - prometaphase - metaphase - anaphase - telophase
  • metaphase spread - In mitosis using light microscope analysis originally used to detect chromosomal abnormalities in cells, as chromosomes are only visible during cell division.
  • microfilament - (MF) cytoskeleton filament normally required for cytoplasmic intracellular transport, motility and cell shape. Named by the actin monomers assembling into the smallest in cross-section of the three filament systems (microtubules and intermediate filaments). This system is disassembled and reassembled as the contractile ring for cytokinesis (cytoplasm division) following cell division mitosis and meiosis.
  • microtubule - (MT) cytoskeleton filament normally required for cytoplasmic intracellular transport and motility. Named by the tubulin monomers assembling into "tubes", and are the largest in cross-section of the three filament systems (microfilaments and intermediate filaments). This system is disassembled and reassembled as the spindle apparatus during cell division.
  • mitochondrial DNA - (mtDNA) multiple copies of a small circular DNA molecule located within the mitochondria matrix. In humans 16,568 bp in length containing 37 genes, originally inherited only from the oocyte (maternal inheritance).
  • mitosis - (M phase) The normal division of all cells, except germ cells, where chromosome number is maintained (diploid). In germ cell division (oocyte, spermatozoa) meiosis is a modified form of this division resulting in reduction in genetic content (haploid). Mitosis, division of the nucleus, is followed by cytokinesis the division of the cell cytoplasm and the cytoplasmic contents. cytokinesis overlaps with telophase.
  • p - chromosome short arm (possibly French, petit) and used along with chromosome and band number to indicate genes located on this arm of the chromosome. The chromosome long arm is identified as q (possibly French, tall) chosen as next letter in alphabet after p. These chromosomal arms are only seen when the chromosome is folded for cell division.
  • polar microtubule - spindle apparatus microtubule (MT) that can arise from either pole and overlap at the spindle midzone. This interdigitating structure consisting of antiparallel microtubules is responsible for pushing the poles of the spindle apart. The other spindle types are astral and kinetochore microtubules.
  • prometaphase - (Greek, pro = before) mitosis term referring to the second stage, when the nuclear envelope breaks down into vesicles. Microtubules then extend from the centrosomes at the spindle poles (ends) and reach the chromosomes. This is followed by metaphase.
  • pronuclear fusion - (Greek, pro = before) the process of the fusion of the two haploid nuclear structures (pronuclei) contributed from the spermatazoa and oocyte to form the first diploid nucleus cell. Can also be called "fusion of pronuclei".
  • pronucleus - (Greek, pro = before; plural, pronuclei) the two haploid nuclei or nuclear structures containing the genetic material from the spermatozoa and the oocyte. These two haploid nuclei will fuse together to form the first diploid nucleus cell, the zygote. Therefore the nuclear structures that exist "before the nucleus", the plural term is pronuclei.
  • prophase - (Greek, pro = before) - mitosis term referring to the first stage, when the diffusely stained chromatin resolves into discrete chromosomes, each consisting of two chromatids joined together at the centromere.
  • prophase I - meiosis term refers to the first phase of meiosis I, which together with meiosis II results in the reductive cell division only occurring gametes. Prophase can be further divided into a number of stages: leptotene zygotene, pachytene, diplotene, diakinesis.
  • q - chromosome long arm (possibly French, tall), the next letter in alphabet after p, and used along with chromosome and band number to indicate genes located on this arm of the chromosome. The chromosome short arm is identified as p (possibly French, petit). These chromosomal arms are only seen when the chromosome is folded for cell division.
  • S phase - during interphase of cell cycle where DNA is duplicated prior to second growth period (G2 phase) that is followed by mitosis (M phase).
  • synapsis - (syndesis) meiosis term for the pairing of two homologous chromosomes that occurs during prophase I.
  • synaptonemal complex - meiosis term for a protein structure essential for synapsis of homologous chromosomes. (proteins SCP3 and SCP1).
  • telomere - region found at each end of the chromosome and involved in cellular ageing and the capacity for division. The regions consist of repeated sequences protecting the ends of chromosomes and harbour DNA repair proteins. In the absence of the enzyme telomerase, these regions shorten during each cell division and becoming critically short, cell senescence occurs.
  • telophase - mitosis term referring to the fifth stage, where the vesicles of the nuclear envelope reform around the daughter cells, the nucleoli reappear and the chromosomes unfold to allow gene expression to begin. This phase overlaps with cytokinesis, the division of the cell cytoplasm.
  • telomerase - the enzyme that maintains the chromosome end length, the telomeres, involved in cellular ageing and the capacity for division. Absence of telomerase activity leads to the chromosome ends shorten during each cell division, becoming critically short and cell senescence then occurs.
  • tetrad - (bivalent) a pair of homologous chromosomes physically held together by at least one DNA crossover.
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Cite this page: Hill, M.A. (2024, March 28) Embryology Trisomy Mosaicism. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Trisomy_Mosaicism

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