Genetic Causes of Down’s Syndrome Essay

Familial Causes of Down ‘s Syndrome

In DS, about 95 % of the instances are due to non-disjunction resulting in an excess transcript of chromosome 21 ( trisomy 21 ) as described by Lejeune et Al. already in 1959 ( Lejeune, Turpin et Al. 1959 ) . The staying is due to translocations affecting chromosome 21 and bodily mosaicism ( Sherman, Freeman et al. 2005 ) .

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The consequence of extra familial stuff nowadays from the excess transcript of chromosome 21 that causes the features of Down syndrome is non wholly clear ( Sarah Hartway, 2009 ) .

There are theories explain this status, one theory is that by holding an excess transcript of chromosome 21, the cistrons nowadays on the chromosome are present in three transcripts alternatively of two, bring forthing 50 % more consequence. This is called the “gene-dosage consequence, ” proposing that cistrons work something like medicines in that a different dose causes a different consequence ( Patterson and Costa, 2005 ; Sarah Hartway, 2009 ) .

Another theory about why the excess familial stuff leads to the features of Down syndrome is that full sets of cistrons may hold higher activity degrees and together lead to the features. These two possible accounts may be right, and both mechanisms may go on at the same time ( Patterson and Costa, 2005 ) .

Table:Chromosomal Abnormalities in Down ‘s syndrome ( Peter et al, 2007 ) .

Chromosomal Abnormalities in Down ‘s syndrome

Frequency ( % )

Trisomy 21



95 %

4 %

1 %

Figure: Typical cell division

  1. Nondisjunction

Nondisjunction is the most prevailing mechanism by which Down syndrome occurs, accounting for approximately 94 % of all instances ( Anna and Mary, 2006 ) . Simply it refers to an mistake in cell division at the clip either the egg or the sperm was formed. The freshly formed egg or sperm has 24 chromosomes, alternatively of the usual 23. In this type of aberrance, the bearer has 47 chromosomes, including three chromosomes 21 ( Thomas and Gesa, 2011 ) .

The bulk of free trisomy 21 instances ( 85-90 % ) originate from mistakes in maternal miosis. In peculiar, maternal miosis I is the most often affected phase of nondisjunction ( & A ; gt ; 75 % ) , whereas maternal miosis II mistakes account for & A ; gt ; 20 % ( Thomas and Gesa, 2011 ) .

In 5 % of free trisomy 21, paternal meiotic mistakes can be observed, here miosis II nondisjunction is more frequent than miosis I errors. In add-on, station zygotic mitotic mistakes have besides been reported ( 5 % ) ( Hulten et al. , 2010 ) .

At construct, the egg or sperm from each parent articulation, ensuing in a fertilized ovum, the package of cells merely following fertilisation of the egg with a sperm, with 47 entire chromosomes. When a neonate is suspected of holding Down syndrome, a blood sample can be taken and tests done to number, kind, and expose the chromosomes in each cell. This is called a karyotype ( Anna and Mary, 2006 ) .

Nondisjunction appears to happen as something of a good luck of nature with a cause that is non yet known. It does non normally occur as a consequence of an familial likeliness, although it does look that some households seem to be prone to mistakes of nondisjunction raising their hazard somewhat ( Al Awadi, et Al. 1998 )

This household inclination is non something that can be tested at this clip, so when a twosome has already had a kid with Down syndrome and is anticipating another kid, they will most probably be told that their hazard of holding a 2nd kid with Down syndrome is about 1 % plus the hazard associated with the mother’s age ( Johnston and Petrakis 2007 ) .

There is some dissension in the literature about this hazard and how to cipher it in portion because the construct of a 2nd kid with Down syndrome as a consequence of nondisjunction to the same parents is really uncommon ( ( Johnston and Petrakis 2007 ) .

Figure: Trisomy 21 ( Nondisjunction ) Cell Division

  1. Robertsonian Translocation

Chromosome translocationis a chromosome abnormalcy caused by rearrangement of parts between nonhomologous chromosomes. A cistron merger may be created when the translocation joins two otherwise separated cistrons, It is detected on cytogenetic or a karyotype of affected cells.

Trisomy 21 due to an imbalanced translocation of chromosome 21 with a hetero- or homologous acrocentric, satellite-bearing chromosome ( 13, 14, 15, 21, and 22 ) is called a Robertsonian translocation ( Thomas and Gesa, 2011 ) .

In DS, Translocation occurs far less often than nondisjunction, accounting for approximately 3 % to 4 % of all instances. Here, all or a portion of an excess transcript of chromosome 21 is present in every cell of the person with Down syndrome, but it is attached to another chromosome ( Jayalakshamma et al, 2010 ) .

Approximately tierce of the instances of translocation Down syndrome occur as a consequence of a parent being a bearer for the translocation. The parent is unaffected and shows no marks of Down syndrome. The other two-thirds of the clip translocation occurs as an stray event and is non inherited ( Anna and Mary, 2006 ) .

Parents who learn that their baby’s Down syndrome occurred as a translocation should be offered familial guidance, even if they do non be after future kids. The possibility of inherited hazard could impact the baby’s siblings every bit good as other relations. These possible hazards can be explained in greater item as portion of familial guidance.

  1. Reciprocal translocations

Reciprocal translocations are caused by the exchange of euchromatic parts of chromosome 21 with the euchromatin of different somatic chromosomes or gonosomes ( M. Oliver-Bonet, 2002 ) . In add-on to trisomic parts in assorted length and location of chromosome 21, unbalanced signifiers at the same clip demo partial monosomy for the exchanged parts of the 2nd translocation chromosome. As a consequence, the phenotype in the bearers of imbalanced translocations is non consistent ( Thomas and Gesa, 2011 ) .

Caused by the rare happening of these translocations, there are no dependable informations for their incidence, a frequence of less than 1:1000 standard trisomies can be assumed ( Schinzel, 2001 ) .

  1. Mosaicism

The incidence of Mosaic Down syndrome occurs really infrequently and histories for merely 1 % to 2 % of all instances of Down syndrome, but likely many are undiagnosed. Peoples with Mosaic Down syndrome have the excess transcript of chromosome 21 in some cells of the organic structure, whereas other cells have the normal two transcripts of chromosome 21 ( Cassidy, et al 2001 ) .

Mosaicism can go on in two different ways. The first mechanism for mosaic Down syndrome is that ab initio the fertilized ovum, the package of cells merely following fertilisation of the egg with a sperm, has 3 transcripts of chromosome 21 in every cell but at some point in cell division, at least 1 cell line someway drops the excess transcript of chromosome 21 ( Fishler and Koch 1991 ) .

The other mechanism for mosaic Down syndrome is that the fertilized ovum has the typical 2 transcripts of chromosome 21 but every bit cell division continues, one of the cells has a duplicate of chromosome 21, once more, for grounds unknown ( Fishler and Koch 1991 ) .

Some research workers have tried to look into links between the grade of disablement and the per centum of trisomic cells that the kid has. For illustration, some kids have merely 25 % of their cells with the excess chromosome while some have 50 % and some have 75 % affected cells. It has been suggested that kids with a lower per centum of trisomic cells ( Sue Buckley and Gillian, 2002 ) .

Mosaicism is normally described as a per centum, if the cytogeneticist counts 50 cells and 10 have a normal cell line and 40 have an excess figure 21 chromosome, so the degree of mosaicism is said to be 80 % . If the per centum of trisomic cells in all bodily tissues is little ( 0.5 – 5 % ) , the phenotype of the bearer can be normal ( Thomas and Gesa, 2011 ) .

While the per centum of mosaicism is normally determined from blood cells, the per centum may really be different in other tissues or parts of the organic structure. For illustration, a individual could hold 80 % mosaicism in their blood cells, but have full trisomy in their tegument or encephalon cells ( Cassidy, et al 2001 ) .

Mosaic Down syndrome may be more hard to name than either nondisjunction or translocation because the features of Down syndrome may non be as apparent right at birth. However, one time Down syndrome is suspected, the blood trial for the karyotype should be done ( Pangalos, 1994 ) .

Normally cells of a different type than blood will be tested, such as tegument or bone marrow to see whether they have 3 transcripts of chromosome 21. If some cell lines, such as tegument cells, Have 3 transcripts of chromosome 21, whereas other cell Lines, such as blood cells, have merely 2 transcripts of chromosome 21, mosaic down syndrome has been identified ( Pangalos, 1994 ) .

On norm, the effects of Down syndrome on people who have nondisjunction or translocation are non perceptibly different. Peoples with Mosaic Down syndrome may hold fewer features or wellness and acquisition challenges than those with either nondisjunction or translocation because non every cell line is affected by excess familial stuff.