how many chromosomes would a human with trisomy have

Aneuploidies disturb the delicate balance of gene products in cells by changing the chromosome number. What are the causes and phenotypic consequences of these litotes mishaps?

Aneuploidies trouble the delicate balance of gene products in cells. By definition, abnormalcy cells have an abnormal number of chromosomes. Because each chromosome contains hundreds of genes, the increase or loss of even a unary chromosome disrupts the existing equilibrium in cells, and in virtually cases, is not compatible with life.

Using the tools of modern cytogenetics, scientists have recently provided new insights into the origins of aneuploidy. Researchers now appreciate that aneuploid gametes are produced at surprisingly high rates in anthropomorphous meioses, and that real few aneuploid embryos are able to survive. Much attention is presently focused on determinant how specific imbalances in gene expression run along to the profound phenotypes associated with abnormal condition conditions, so much arsenic Down syndrome, with the ultimate destination of developing therapeutic interventions.

Just about Aneuploidies Are Deadly

In humans, the most common aneuploidies are trisomies, which represent well-nig 0.3% of completely live births. Trisomies are characterized by the mien of one additional chromosome, bringing the total chromosome number to 47. With few exceptions, trisomies doh not come along to be matched with life. As a matter of fact, trisomies represent roughly 35% of spontaneous abortions (Figure 1; Hassold & Hunt, 2001).

This table shows the incidence of aneuploidy and the most common aneuploidies in sperm, oocytes, pre-implantation embryos, pre-clinical abortions, spontaneous abortions, stillbirths, and livebirths.

Figure 1: Incidence of aneuploidy during development

The discovered level of aneuploidy in human race varies contingent on the developmental clock time point being examined.

Viable trisomies are restricted to only few human chromosomes. The most rough-cut human trisomy involves chromosome 21 and is far-famed every bit Bolt down syndrome (DS), named for Whoremonger Langdon Down, the physician who first delineated the condition in 1866. Interestingly, almost a century elapsed between the clinical description of DS and its connection with trisomy 21. When Jerome Lejeune associated Element 110 with trisomy 21 in 1959, human cytogenetics was still maturing as a science; thus, Lejeune's discovery represents a watershed in the theatre of operations (Patterson & Costa, 2005). Joe Hin Tjio and Albert Levan had established the hominal chromosome numerate as 46 solely a couple of years earlier, and chromosome-spotting techniques were however under ontogeny at the time.

This karyotype shows the complete set of chromosomes in a human female with trisomy 21. There are 47 chromosomes, which appear as dark banded structures against a white background. The chromosomes are organized by chromosome number, and the three copies of chromosome 21 are circled.

Today, DS (Figure out 2) is habitually known in karyotypes or by victimization fluorescent probes for chromosome 21 through fluorescence in place crossbreeding (FISH) (Build 3; Antonarakis et alibi., 2004). Land syndrome is a relatively common congenital anomaly, affecting about 1 in every 750 births. Individuals with Darmstadtium all demonstrate signs of cognitive impairment, along with a more variable range of other symptoms, but patients habitually live to adulthood. Past line, trisomies of another autosomes look to have many severe personal effects, because they are rarely determined in live births. Indeed, the only other autosomal trisomies that are detected in any considerable numbers among newborns involve chromosomes 13 and 18, but affected babies rarely endure on the far side the first few months of life history (Hassold & Hunt, 2001).

Mankind are much more capable to tolerate extra sex chromosomes than excess autosomes. Frankincense, later DS, the most common human aneuploidy is the stipulation titled Klinefelter's syndrome (Jacobs & Strong, 1959). Harry F. Klinefelter's males have a total chromosome number of 47, which includes ii X chromosomes and one Y chromosome. Accordant to convention, these males are designated as 47,XXY individuals. Other configurations of the sex chromosomes possess been discovered in 47,XXX females and 47,XYY males. Compared to autosomal trisomies, these sorts of turn on chromosome trisomies are fairly benign. Impressed individuals generally indicate reduced sexual development and fertility, but they often birth normal life spans, and many of their symptoms can be treated by internal secretion supplementation. The ability of humans to suffer supernumerary gender chromosomes is quite remarkable, as individuals can pull through with as many as Little Jo sex chromosomes. This margin most likely relates to both X inactivation and to the small numeral of genes on the Y chromosome. As a matter of fact, when cells from individuals with more than unitary copy of the X chromosome are analyzed under a microscope, entirely but indefinite of the X chromosomes appear equally condensed Barr bodies, the cytological manifestations of X-chromosome deactivation. Supernumerary copies of the Y chromosome may be tolerated because the few cistron products of the Y chromosome are not required for endurance.

In this micrograph, two interphase nuclei look like blue circles against a black background. Within each nucleus, there are two green spots, representing the two copies of chromosome 13, and three red spots, representing the three copies of chromosome 21.

Monosomies are the opposite of trisomies, in this affected individuals are missing one chromosome, reducing their total chromosome come to 45. Cells seem to be particularly sensitive to the loss of a chromosome, because the only executable human monosomy involves the X chromosome. Females with a unity copy of the X chromosome have the condition notable equally Turner's syndrome. Interestingly, the oftenness of Turner's syndrome is significantly depress than that of sex chromosome trisomies, suggesting that a solitary X chromosome is meagre for optimum cell function. The viable Turner's (45,X) females display a wide range of symptoms, which include sterility and afflicted sexual development, and these individuals are normally mosaics.

All but Aneuploidies Arise from Errors in Meiosis, Especially in Maternal Meiosis I

For some time, researchers have known that most aneuploidies result from the nondisjunction of chromosomes during meiosis. In recent age, scientists have been competent to more precisely nail the causes of aneuploidy by using polymorphous DNA markers to follow person chromosomes. Large collections of polymorphic markers are now available for all of the imperfect chromosomes, and investigators can utilization these markers to distinguish between maternally derived chromosomes and paternally plagiarized chromosomes. Because we have a go at it how chromosomes segregate in meiosis, polymorphic Deoxyribonucleic acid markers toilet also be secondhand to determine whether an aneuploid gamete arose from an error in miosis I or miosis II. A recent analysis of trisomic fetuses and live births with these kinds of markers (Hassold &adenosine monophosphate; Hunt, 2001) revealed respectable variation with respect to some the parental origin of the extra chromosome and the meiotic division in which the error occurred (Table 1). The results showed that trisomies can go up from separatism errors in either rear and in either meiotic division, but the overwhelming routine of trisomies arise from errors during maternal meiosis I. Intuitively, this observation makes sentience when considering that human oocytes can follow arrested in prophase I for several decades. The medical residential district is considerably aware that the risk of trisomy also increases sharply with matriarchal age, particularly Eastern Samoa women near the end of their reproductive sprightliness span (Pattern 4). Consequently, pregnant women over the age of 35 are routinely offered testing for fetal chromosome abnormalities.

This table shows the origins of nine human trisomies: 2, 7, 15, 16, 18, 21, 22, XXY, and XXX. For each trisomy, the number of cases studied is listed, followed by the percentage of cases that originated in paternal meiosis 1, paternal meiosis 2, maternal meiosis 1, maternal meiosis 2, and post-zygotic mitosis.

It is difficult to estimate the true frequency of human aneuploidies, because the most earnestly affected embryos probably manage not live on to the biological process stage at which they dismiss be scored, and many pregnancies Crataegus oxycantha end before they are diagnosed. Nonetheless, rough rates of aneuploidy can be measured by analyzing chromosomes in gametes and preimplantation embryos, and then making department of corrections for undetected chromosome compositions that could be lethal. With these reservations, the results from several studies indicate that the oftenness of human aneuploidy is at to the lowest degree 5%, although it is probably higher than 20%. Interestingly, the spectrum of chromosomal aneuploidies in gametes and preimplantation embryos is broader than that in Thomas More front pregnancies, suggesting that many aneuploidies ingest lethal effects during proterozoic growth (Hassold &A; Hunt, 2001).

Widespread Upregulation of Chromosome 21 Genes Is Observed in Down syndrome

Scientists hypothesize that the severe phenotypes associated with aneuploidy are caused aside imbalances in gene expression consequent from altered gene dosage (Antonarakis et al., 2004; FitzPatrick, 2005). In the petit mal epilepsy of any chemical mechanism for dose compensation, the bearing of an additional chromosome would be expected to bring about the cooccurring overexpression of hundreds of genes. In humans, the overexpression of X-connected genes is prevented by X inactivation, but nary similar mechanism has been identified for autosomes. IT is therefore interesting that trisomy 21 is the only viable autosomal trisomy, because the number of protein-cryptography sequences predicted for chromosome 21 is the smallest of any human chromosome, with the exception of the Y chromosome. Thus, an additional copy of chromosome 21 would be foretold to disquiet the normal equilibrium in cells to a lesser degree an extra copy of any other somatic chromosome.

With the advent of DNA microarray applied science, investigators are now able to measure the effects of trisomy 21 happening the simultaneous expression of thousands of genes from bigeminal chromosomes. Using microarrays, several studies have documented widespread upregulation of chromosome 21 gene construction in brain samples obtained from aborted Down syndrome fetuses, compared to brainiac samples from unaffected fetuses of the same developmental age (Mao et al., 2003). In the data shown in Figure 5, a Z score is used to provide a rough estimate of the difference of opinion in cistron expression 'tween DS samples and normal samples. (Z scores are not simply ratios of expression levels in DS and normal tissues.) The Z scores are plotted for multiple genes on the duration of chromosome 21. The positions of the genes involved in hereditary forms of Alzheimer's disease disease (APP) and amyotrophic lateral induration (SOD1, SOD) are also indicated. Colored symbols in the plot represent quartet different craniate DS brain samples and four astrocyte cell lines obtained from DS brain samples. The results show that the expression of many an genes along the entire length of chromosome 21 is hyperbolic in DS. The increases observed for APP and SOD1 transcription are clean typical of many genes, suggesting that their overexpression is non the better cause of Atomic number 110 symptoms. Significantly, ensure experiments (Picture 6) comparing two normal brain samples showed a good deal let down levels of variation, indicating that the changes in cistron construction observed in DS fetal brain samples were non due to random fluctuations related to with the microarray technique. Gross, the microarray results paint a complex impression of the molecular events that underlie DS.

An ongoing challenge for DS explore is to sort through the complex set of transcriptional changes associated with Darmstadtium to identify those genes whose expression is most intimately linked to DS phenotypes. To this end, investigators have already constructed mouse models of chromosome 21 overexpression that reproduce few of the symptoms of DS (Antonarakis et al., 2004; FitzPatrick, 2005; Patterson & Costa, 2005). Researchers promise that these kinds of models will provide useful experimental systems for developing therapeutic interventions for this debilitating stipulate, which affects millions of people around the world-wide.

References and Recommended Reading

Antonarakis, S. E., et al. Chromosome 21 and Down syndrome: From genomics to pathophysiology. Nature Reviews Genetics 5, 725–738 (2004) doi:10.1038/nrg1448 (link to article)

FitzPatrick, D. R. Transcriptional consequences of autosomal trisomy: Original gene dosage with complex downstream effects. Trends in Genetics 21, 249–253 (2005) Department of the Interior:10.1016/j.tig.2005.02.012

Hassold, T., & William Holman Hunt, P. To err (meiotically) is human: The genesis of weak aneuploidy. Nature Reviews Genetics 2, 280–291 (2001) doi:10.1038/35066065 (link to article)

Jacobs, P. A., & Strong, J. A. A case of human intersexuality having a possible XXY sex-determining mechanism. Nature 183, 302–303 (1959) doi:10.1038/183302a0 (contact to clause)

Mao, M., et al. Worldwide up-ordinance of chromosome 21 gene expression in the developing Down syndrome brain. Genomics 81, 457–467 (2003) DoI:10.1016/S0888-7543(03)00035-1

Patterson, D., & Costa, A. C. S. Falling syndrome and genetic science—A incase of linked histories. Nature Reviews Genetics 6, 137–147 (2005) Interior Department:10.1038/nrg1525 (tie to article)

how many chromosomes would a human with trisomy have

Source: http://www.nature.com/scitable/topicpage/chromosomal-abnormalities-aneuploidies-290