How Many Chromosomes Can a Gamete Possess as a Result of Nondisjunction
Revista Salud Uninorte
Print version ISSN 0120-5552 On-line version ISSN 2011-7531
Salud, Barranquilla vol.26 no.1 Barranquilla Jan./June 2010
ARTÍCULO DE REVISIÓN / REVIEW ARTICLE REVISIÓN BÁSICA / BASIC REVIEW Nondisjunction and chromosomal anomalies La no disyunción y las anomalías cromosómicas Mostapha Ahmadone, Silvera-Redondo C.1, Muna Hamdan Rodrígueztwo 1 Grupo de Investigación Genética y Medicina Molecular, Universidad del Norte, Barranquilla (Republic of colombia). mahmad@uninorte.edu.co ii Departamento de Enfermería, Universidad del Norte, Barranquilla. munahamdan85@gmail.com Correspondencia: Universidad del Norte, Km 5 via a Puerto Republic of colombia, Barranquilla (Colombia). Fecha de recepción: 2 de febrero de 2010 Resumen La no segregación es el fracaso de los cromosomas homólogos en separarse correctamente durante la meiosis. Esto resulta en la producción de gametos que contienen una cantidad de cromosomas mayor o menor a la encontrada en una célula normal. Consecuentemente, el individuo puede desarrollar una trisomía o monosomía. La no disyunción puede ocurrir en meiosis I o meiosis II de la división celular, es una causa de diversas condiciones médicas anormales, incluyendo el Síndrome de Downwards (trisomía del cromosoma 21), Síndrome de Patau (trisomía del cromosoma 13), Síndrome de Edward (trisomía del cromosoma 18) y Síndrome de Turner (la presencia de united nations solo cromosoma X). A pesar de que es la causa de numerosos trastornos genéticos, aún no se conoce su etiología exacta y el proceso en el cual se lleva a cabo. La no disyunción se origina en el mayor de los casos de errores en la meiosis II materna, sin embargo, la meiosis paterna y la meiosis I materna influyen en ella. La edad materna se considera como un factor de riesgo de las trisomías, igual que la alteración de la recombinación y otros factores que pueden afectar la segregación cromosó-mica, tal como la genotoxicidad y translocaciones cromosómicas. Esta revisión se realizará con base en artículos publicados entre 2003 y 2009 en ISI Web, Science Directly, PUBMED, SPRINGER y SCIELO; se interpretará y analizará en ella los resultados de estos estudios que lograron demostrar conclusiones importantes y sobresaltaron factores interesantes que pueden ser el punto de partida para próximas investigaciones. Palabras clave: No disyunción, monosomía, trisomía, miosis, mitosis, recombinación, síndrome, genotoricidad, mutación cromosómica. Abstruse Nondisjunction is the failure of homologous chromosomes to disjoin correctly during meiosis. This results in the production of gametes containing a greater or lesser chromosomal corporeality than normal ones. Consequently the individual may develop a trisomal or monosomal syndrome. Not disjunction can occur in both Meiosis I and Meiosis II of the cellular partition. It is a cause of several abnormal medical conditions, including Downward'south syndrome (trisomy of chromosome 21), Patau'southward Syndrome (trisomy of chromosome 13), Edward's Syndrome (trisomy of chromosome eighteen) and Turner'south Syndrome (the presence of but i X chromosome). Information technology is also the main cause of many genetic disorders, however its origin and procedure remains vague. Although it results in the majority of cases from errors in the maternal meiosis Two, both paternal and maternal meiosis I do influence it. The maternal age, is considered a risk factor of trisomies, also every bit recombination alterations and many others that tin can affect the chromosomal segregation, such as genotoxicity and chromosomal translocations. We will review the results of previously realized studies between the years 2003 and 2009, found in ISI WEB, PUBMED, SCIENCE Direct,SPRINGER LINK and SCIELO, that led to of import conclusions and highlighted interesting factors that can be the starting point to futurity investigation. Key words: Nondisjunction, monosomy, trisomy, Meiosis, Mitosis, Recombination, Syndrome, genotoxicity, chromosomal mutation. INTRODUCTION Investigators have been studying the aneuploids man conditions afterward the description of the offset instance of trisomy 21 (Down syndrome) on 1959 by Lejeune and Patricia Jacob. They focused their investigation and studies on the genesis of this aberrant condition developed past humans. Recently, aneuploidy was likewise confirmed experimentally as a dominant mutator, independent of gene mutation in other eukaryotes, including Drosophila, yeast, plants, and mice. These studies were centered in searching about iii basic things; the frequency of aneuploid conditions, the reason of gaining (extra) or loosing (less) chromosomes and the nondisjunctional mechanism that gives rise to aneuploid conditions. Despite the technological evolution and the number of realized studies in aneuploid genesis, investigators still don't have articulate answers to the second and the third interrogates, however the offset i has been answered. The frequency of aneuploid weather condition which is amazingly common and clinically important in our species is estimated in approximately 5% of clinically recognized pregnancies (i). Therefore we will effort to recombine all the results of previous studies, in guild to reach a conclusion that defines the causes of chromosomal nondisjunction and answer the question wheather maternal historic period is its simply trigger or in that location are still other factors behind information technology? HOW DOES NONDISJUNCTION OCCUR? Nondisjunction is the miss segregation of a homologous pair of chromosomes during meiosis (figure one). It leads to the formation of a new cell with an abnormal amount of genetic fabric. A number of clinical atmospheric condition are the consequence of this type of chromosomal mutation. Homologous chromosomes are identical chromosomes that can be observed in pairs, in which 50 °% of this amount is inherited from each parent. Humans have 46 chromosomes, or 23 homologous pairs. Usually, in meiois the homologous chromosomes attach to spindle fibers (figure ii), which connect the 2 centrioles and become aligned at the prison cell equator. Before the first meiotic partition takes identify the homologous pairs migrates to the jail cell's opposite poles by means of the pulling activity of the spindle fibers, and upon meiosis completion each gamete volition have one copy of every chromosome. Nonetheless, this process can suffer some errors that lead to homologous chromosomes separation failure and thus both migrate to the same pole (effigy 3). Consequently two types of gametes are produced, 1 of which has two chromosomal copies, whereas the other lacks one. A zygote which has a chromosome less than the normal diploid amount (2n-ane) is called monosomic, and that which has an actress chromosome (2n+ane) is trisomic, both conditions may develop severe abnormalities that can be fatal (1). CAUSES AND FREQUENCY OF NONDISJUNCTION IN HUMANS Meiosis is a process that consists of a number of cheque points that regulate prison cell division in all its phases to ensure that the cells will divide and give rise to new ones correctly without whatsoever fault. In example an error occurs these regulating points must correct it. One of these check points is the spindle fibers checkpoint which is responsible of three principle steps; formation of these spindle fibers, the attachment of chromosomes to them and the adequate segregation of these chromosomes. When whatever bank check point fails in realizing its correct function, it leads to nondisjunction, as a outcome of the incorrect segregation of the homologous chromosomes. Despite the insufficient studies about the causes of nondisjunction, it is known to occur more oft in older cells. This is why older women may requite birth to bear on off springs due to an aneuploid aberration more than immature ones. The adventure of a xx-years-old female parent giving nascency to a child with Down syndrome is almost i in two k and it increases to i in thirty in the example of a xl-v years old woman. This hypothesis depends on a unproblematic elucidation that in older cells the regulating system does not office as in younger cells and as a consequence the cell will lose the control. Thus an older prison cell undergoing meiosis would be more probable than a younger one to ignore the constraints of the spindle checkpoint and hence give rise to aneuploid cells. This was confirmed by a written report done in patients with Down's syndrome which demonstrated that the incidence of this syndrome was elevated with increased maternal age. Many specialists recommend that women who go pregnant at age 35 or older must undergo prenatal testing for Down's syndrome. The probability of pregnant fewer than 30 to requite birth to a babe with Down's syndrome is less than 1 in 1,000, but the chance of having a baby with Down's syndrome increases to 1 in400 in women who become pregnant at historic period 35. The likelihood of Downwardly syndrome continues to increment as women ages exercise, so that past historic period 42, the chance is 1 in sixty and by age 49, the adventure is i in 12. But using maternal age lone will not detect over 75% of pregnancies that upshot in Downwardly syndrome (10). No disjunction doesn't only relate with maternal weather condition, but also with paternal and mitotic conditions. A study verified that trisomy 21 was 90.ix% maternal, iv.5% paternal and 4.5% from a mitotic origin; similar to distributions reported previously (iv). Information technology besides confirmed that nondisjunction doesn't only take identify in meiosis II but also in meiosis I (MI: 46.1%, MII: 53.9%).Even though it was established by other studies that MI is lxx% and MII is 30% related to Down's syndrome, information technology was reported that what causes it in 88% of cases is the extra copy of chromosome 21 derived from the mother, in 8% of the cases the begetter provided the extra copy of chromosome 21 and in the remaining 2% Down syndrome is due to mitotic errors; an error in cell division which occurs after fertilization when the sperm and ovum are joined (10). Information technology was also reported in 82 patients with trisomy 13 that the parental origin was determined in every example and in 89% the extra chromosome thirteen was of maternal origin with an most equal number of maternal MI and MII errors (8). Until here we achieved to demonstrate that nondisjunction is from maternal, paternal and mitotic origin, the distinctive difference are the frequencies and percentages as we tin encounter briefly in the table beneath. Adapted from Hall et al. (vi). MI, meiosis I; MII, meiosis II; PZM, postal service-zygotic mitotic (xi). The direct exposure to loftier levels of genotoxic gaseous and particulate substances from the engines combustion used in motor vehicles is required by sure type of occupations. These occupational exposures may convert into an important cause of many illnesses, usually through chromosomal changing mechanisms that include strand breakage, deletions, sister chromatid commutation and not-disjunction. To decide the consequence of occupational exposure in gasoline station attendants and traffic enforcers, the micronucleus exam was used in three groups: gasoline station attendants, traffic enforcers and a group of control. A study showed no relation betwixt MNC frequency and whatsoever of the factors such as age, smoking habits, alcohol habits and working period. This was further confirmed in the multiple regression analysis which showed that only occupational exposure was a practiced predictor of MNC frequency. The results of this report suggest that gasoline station attendants and traffic enforcers, compared to the control individuals, are at a greater risk of chromosomal damage. For the assessment of chromosomal damage, the study, evolution, and standardization of tests are recommended for public institutions concerned with matters regarding environmental quality and community health (12). Information technology was as well shown in six males(13), carriers of Robertsonian translocation that higher incidences of aneuploid sex chromosomes in spermatozoa were institute in 3 Rob translocation carriers, which indicated that the ICE (interchromosomal result) on sex chromosome is likely in some male carriers of Rob translocations. This report suggests that genetic counseling is of import for the carriers of Rob translocations. In guild to maximize the chances of normal pregnancy, they highly recommend that normal or balanced embryo should be selected for transfer by preimplantation genetic diagnosis analysis of translocation chromosome, accompanied with a preimplantation genetic screening for sexual activity chromosome aneuploidy (13). On the other hand meiotic origin and the stage of non-disjunction of the actress Ten chromosomes in two sisters with 47, XXX chromosomal complements were studied (14) and demonstrated that the lack of recombination in the X chromosomes suggests a possible maternal genetic defect leading to an erratic recombination at MI. This data may contribute to farther understanding of mechanisms leading to Ten chromosome non-disjunction and may assist in counseling of families with this chromosomal rearrangement (14). CHROMOSOMAL MUTATION AND ITS Classification Chromosomal mutations are variations from the wild-type condition in either chromosome structure or chromosome number. Variation in chromosome number includes aneuploids, which do not involve whole sets of chromosomes (genomes) but only parts of a set (genome) (aneu-uneven; ploid-unit). They may be of the following types: Monosomy; diploid organisms which lack i chromosome of a unmarried homologous chromosome pair are called monosomics and accept the genomic formula 2n -one. A monosomic produces ii kinds of gametes (n) and (n-l), every bit the unmarried chromosome missing a pairing partner may travel to either pole during meiosis. In plants north -1 gametes remain non-functional, whereas in animals they result in genetic imbalance which is manifested by high mortality or reduced fertility. Nullosomy; diploid organisms which have lost a pair of homologous chromosomes are called nullosomics and posses the genomic formula 2n-two. The nul-losomics exhibit reduced vigor, fertility and survivability, but polyploidy nullosomics such as nullosomic hexaploid, having (6n-two) survive to maturity due to the genetic back-up in polyploidy. Trisomy; diploid organisms which accept one extra chromosome are called trisomies. They have the chromosomal formula 2n+1. In a trisomic, one of the chromosomal pairs has an extra member, forming a trivalent structure during meiosis. During anaphase, two chromosomes travel to one pole and the tertiary to another. Thus, two types of gametes north + 1 and n are resulted. Trisomy has variable effects on the phenotype of the organism. In humans trisomy of autosome 21 causes Down syndrom. Tetrasomy, it results when one chromosome of a diploid organism is present in quadruplicate. Tetrasomics have the chromosomal formula twenty+2. During meiosis a quadrivalent is formed by extra chromosomes and segregation of chromosomes occurs like autotetraploids. Double Trisomy; in a diploid organism when two different chromosomes are represented in triplicate, double trisomy results. A double trisomic has the chromosomal formula 2n+1+i. Although euploidy (eu-truthful or fifty-fifty; ploid-unit of measurement) designates genomes containing whole sets of chromosomes, it is very important to distinguish between aneuploid conditions mentioned previously and mixoploidy (mosaics), which refers to the presence of two jail cell lines, ane diploid and the other polyploid. Though polyploidy in humans is not viable, mixoploidy has been found in live adults and children. Mixoploidy consists of two types: diploid-triploid mixoploidy, in which some cells have 46 chromosomes and others accept 69. Diploid-tetraploid mixoploidy, is characterized by cells having 46 chromosomes and others having 92. Euploids are organisms that posses balanced ready or sets of chromosomes or genomes in any number, in their body cells. Euploidy is of the following types: Monoploidy, in this case organisms take 1 genome (northward) in their torso cells. When monoploidy occurs in gametes (sperms and eggs) it is termed every bit haploidy. Diploidy, is characterized by ii genomes (2n) in each somatic jail cell of diploid organisms. Virtually animals and plants are diploids. Diploidy is related with fertility, balanced growth, great vigorosity, adjustability and survivability of the diploid organisms. Polyploidy is the status where organisms have more than than two genomes. Among plants and animals, polyploidy occurs in a multiple series of 3, 4, 5, half dozen, 7, 8, etc., of the bones chromosome or genome number and thus causes triploidy, tetraploidy, pentaploidy, hexaploidy, heptaploidy, octaploidy, respectively. Ploidy levels higher than tetraploid are not ordinarily encountered in natural populations, but our nigh important crops and attractive flowers are polyploidy, e.g., wheat (hexaploid, 6n), strawberries (octaploid, 8n), many commercial fruit and attractive plants, liver cells of homo, etc. Variation in chromosomal structure includes deletion (loss), duplication (proceeds), inversion (a segment of a chromosome is reversed end to cease), and translocation (exchange segments). These mutations in chromosomal structure are caused by unequal crossover and/or abnormal segregation of chromosomes during mitosis. Unbalanced chromosomal rearrangement has loss or gain of genetic material, which may causes phenotype disorders or diseases. Counterbalanced chromosomal rearrangement may also cause mutations through changes in gene expression. LETHAL AND Not-LETHAL Human ANEUPLOID CONDITIONS Aneuploid atmospheric condition are divided into lethal and nonlethal. Lethal aneuploid atmospheric condition are related to cistron dose and its importance in the evolution. Each normal jail cell contains 46 chromosomes (one pair of sex chromosomes that tin can be Xx in females or XY in males and 22 pairs of autosomal chromosomes). In order to develop appropriately, the cell must incorporate the correct dose of genes and each gene in its right position. A change in the gene dose and position tin occur by removing or calculation chromosomes to the normal set resulting in disproportion and developmental problems. Not all cistron duplication or silencing cases are lethal; it is the addition or loss of a chromosome that contains g or more genes, that results in lethality. Downwardly syndrome, acquired past trisomy 21 is an case that demonstrates the cell's tolerance to small-scale changes but not to big ones. Chromosome 21 contains a minor number of genes for it is one of the smallest chromosomes, thus any change in information technology will not atomic number 82 to mayor effects approval why Down syndrome is not a lethal condition. On the contrary, when a large amount of genes contained past large chromosomes is involved, it may be lethal, this occurs mainly with autosomal chromosomes, where as in sex chromosomes it is less probable. The X chromosome can illustrate such condition, despite of its big size only one is involved in the female development. On other manus, the Y chromosome contains a few genes but is indispensable in male evolution. From these explanations we tin can understand that in some weather condition where the sexual practice chromosomes are involved lean not to be lethal, notwithstanding, the YO status is fatal due to the lack of the essential Ten chromosome. Down syndrome, described for the first time by Jerome Lejeune and Patricia Jacobs in 1959 is the most important non-fatal trisomy in humans. Acquired by the presence of an actress copy of chromosome 21(figure 4), it gives rise to an extra set of genes leading to an over expression of the involved ones and an increase in the product of certain products. For most genes, their over expression has little effect due to the body's regulating mechanisms of genes and their products, but those causing Down's syndrome appear to be an exception. They are Superoxide Dismutase DOS1 ( its over expression may cause premature aging and decreased function of the immune arrangement and its role in Senile Dementia of the Alzheimer's type or decreased knowledge is still speculative)(2), COL6A1( its over expression may exist the crusade of heart defects) (2), ETS2 ( its over expression may be the cause of skeletal abnormalities) (ii), CAFA1( its over expression may be detrimental to DNA synthesis)(2), Cystathione Beta Synthase or CBS and GART (their over expression may disrupt Deoxyribonucleic acid metabolism and repair ) (2), DYRK ( its over expression may be the cause of mental retardation) (2), CRYA1( its over expression may be the cause of cataracts ) (2), IFNAR or the factor coding for Interferon( its over expression may interfere with the immune system besides equally other organs)(2). Other genes that besides stand for suspects in clude APP, GLUR5, S100B, TAM, PFKL, too few others that are non existence mentioned (2). Over again, it is important to notation that no gene has yet been fully linked to any feature associated with Down syndrome (2). Down's syndrome is an example of an au-tosomal trisomy as it involves autosomal chromosome 21 (3). It is reported that trisomy 21(effigy five & 6) is xc.nine% maternal, 4.5% paternal and 4.5% from a mitotic origin (four). At that place are articulate differences in the frequency of maternal meiotic errors as reported in distinct studies. Ramirez et al. (4 ) reported that 46.1% of these errors originate from meiosis I and 53.ix% from meiosis II, on the other hand a previous one encountered that seventy% of the errors resulted in meiosis I and 30% in meiosis 2. Multiple correspondence analyses showed association of either local recombination events or absence of recombination with specific non-disjunction stages. Recombination patterns reported by Ramirez et al. (4) support the hypothesis that susceptible chiasmate configurations are associated to maternal meiosis I and meiosis II errors. Similarly, it was reported in other studies, using Dna polymorphisms to identify the origin of the extra chromosome 21(5). In the largest meta-analysis study of 807 Down syndrome patients, the parental origin was maternal in 90.7% of cases, paternal in 5.5% and mitotic in the remaining 3.8% (six). Additionally, when pericentromeric microsatellite markers were used to find the meiotic stage of nondis-junction, 76% of maternal cases were institute to occur at meiosis I (MI) and 24% at meiosis Two (MII); in the cases of paternal origin, a 1:1 ratio between stages was constitute, with a slight excess of MII errors (7). Trisomies can also affect another autosomal chromosomes, such as trisomy thirteen(Patau syndrome), trisomy 18 (Edwards syndrome), trisomy 15, trisomy 16 and trisomy 22. A written report washed past Merete B et al (eight), which included 82 patients affected by trisomy 13, reported that the parental origin was determined in every case and in 89% the actress chromosome xiii was of maternal origin with an almost equal number of maternal MI and MII errors. There was evidence for elevated maternal age in cases with maternal meiotic origin for born-live infants. Maternal and paternal ages were elevated in cases with paternal meiotic origin. This comes in contrast to results from a similar written report of trisomy 21 non-disjunction, where paternal but non maternal historic period was elevated (6). Clear evidence for reduced recombination was found in both maternal MI and MII errors where the crusade was associated with a significant number of tetrads (33%) that are nullichiasmate, which does non appear to be a feature of chromosome 13 normal meiosis. Merete B et al support in their study (8) the prove for subtle chromosome-specific influences on the mechanisms that determine non-disjunction of human being chromosomes, consequent with the multifariousness of findings for other trisomies. GENETIC DISORDERS Caused BY ROBERTSONIAN TRANSLOCATION, MOSAICS AND Band CHROMOSOME Some syndromes issue from mosaics or Robertsonian translocation. Robertsonian translocation is a common and meaning type of chromosome rearrangement that is formed by fusion of the whole long arms of two acrocentric chromosomes (chromosomes with the centromere near the very cease). They are likewise known as whole-arm or axial-fusion translocations or rearrangements. Robertsonian translocations are named for the American insect geneticist West.R.B. Robertson who commencement described this form of translocation in the grasshoppers in 1916. 1 in almost 900 babies is born with a Robertsonian translocation making it the most common kind of chromosomes rearrangements known in humans. All 5 of the acrocentric chromosomes in humans (chromosome number 13, 14, 15, 21 and 22) have been found to appoint in Robertsonian translocations. The formation of Robertso-nian translocations was discovered past Hecht and coworkers to be highly nonrandom. In balanced course, a Robertsonian translocation takes place between two acrocentric chromosomes and results in no problems for the person conveying it. But in unbalanced form, Robertsonian translocations produce chromosome imbalance and crusade syndroms of multiple malformations and mental retardation. Robertsonian translocations between chromosomes 13 and 14 lead to trisomy xiii (Patau) syndrome. Robertsonian translocations betwixt chromosomes 14 and 21 and betwixt 21 and 22 practice also upshot in other syndroms. Ordinarily, when an egg and a sperm are joined at conception, a single prison cell is created with a total of 46 chromosomes. These chromosomes are copied, the copies are separated, and the jail cell then divides to create two identical "daughter" cells. The chromosomes in these two cells are copied, the copies divide, and four cells are created. These four cells become viii cells. Eight cells go 16 cells, and so on. If nothing disrupts the chromosome replication and separation process, each cell in the trunk should take the same number of chromosomes that were present in the fertilized egg. However, errors can occur in this replication and separation process. Two mechanisms have been proposed to explain why a child may exist built-in with mosaic Down syndrome. The most likely caption is that an extra re-create of chromosome 21 was present in the egg or the sperm at the time of formulation. However, shortly after conception, an error occurred in the chromosome replication and separation process, and the extra copy of the chromosome 21 was not passed on to both cells. In this mode, a second cell group was created with just 46 chromosomes. If this error in the chromosome replication and separation process occurred at the 4 cell phase, 1/four of the cells would take 46 chromosomes and 3/iv would accept 47 chromosomes. If the fault occurred at the 8 cell stage, 1/eight of the resulting cells would have 46 chromosomes and 7/8 would have 47. Information technology is also possible that a kid with mosaic Down syndrome inherited a total of 46 chromosomes at the time of conception. If this was the case, then the mistake in chromosomal separation, which resulted in the formation of a second jail cell grouping with an extra chromosome 21, occurred early in the baby's development, this is the mosaics which can result also in other syndromes like Patau syndrome, Turner syndrome, etc. On the other hand, many genetics disorders may ascend from ring chromosome, which is a chromosome whose artillery have fused together to form a band. A ring chromosome is denoted by the symbol r. Ring chromosomes may course in cells following genetic damage by mutagens like radiation, they may besides arise spontaneously during development. Although ring chromosomes are very rare, they accept been found in nearly all human being chromosomes. Disorders arising from the formation of a ring chromosome include ring chromosome 20 syndrome where a ring formed past one copy of chromosome 20 is associated with epilepsy. Band chromosome 14 and ring chromosome thirteen syndrome are associated with mental retardation and dys-morphic facial features. Ring chromosome fifteen is associated with mental retardation, dwarf-ism and microcephaly. Ring formation of an X-chromosome causes Turner syndrome. Symptoms seen in patients carrying band chromosomes are more than likely to be caused by the deletion of genes in the telomeric regions of affected chromosomes, rather than past the formation of a ring structure itself. Abnormalities in the autosomal chromosomes is non the simply issue of non disjunction, sometimes the sex activity chromosomes will too exist involved and impact the private'southward secondary sexual characteristics and fertility. For example, Klinefelter's syndrome, in which only the gonosomal chromosomes are affected and the autosomal ones are normal. Information technology results from of the fusion of an XY sperm with a normal X egg, or the fusion of a Y sperm with an Twenty egg. Individuals afflicted by Klinefelter's syndrome, ordinarily accept beneath-average intelligence (effigy seven) (iii). 75% of these individuals present the karyotype 47, XXY (effigy 8). Approximately 20% of the cases result from chromosomal mosaicism which is the major cause represented in 46, XY/47, XXY. Other variants including 48, XXYY, 48, XXXY, and 49, XXXXY be in 5% of the cases (3) that were first described by Fraccaro and Lindsten in 1960. Orit R et al. reported the determination of the meiotic origin and the stage of non-disjunction of the extra Ten chromosomes in two sisters with 47, XXX chromosomal complement (9). Segregation of the X chromosomes in all family members was analyzed using X-linked short tandem repeat polymorphic (STRP) markers. Densitometric analysis of two STRP markers confirmed that both sisters had three copies of the X chromosome and the extra 10 chromosomes were maternally derived. Both sisters did not share the same maternal homologue, suggesting that the recurrent trisomy is non-homologous X chromosome-specific. Haplotype analysis demonstrated a reduction to homozygosity for markers examined, covering most of the length of the X chromosomes in both sisters. These findings suggested that the extra X chromosomes take derived from meiotic 2 non-disjunction following a null transitional meiosis I (MI). A lack of recombination in the X chromosomes of both sisters suggests a possible maternal genetic defect leading to an irregular recombination at MI. This data may contribute to farther understanding of mechanisms leading to X chromosome non-disjunction and may aid in counseling of families with this chromosomal rearrangement (9). Individuals with Turner'due south syndrome (XO) are females with a single X chromosome. They are sterile, possess underdeveloped secondary sexual characteristics and they are shorter than normal. This condition occurs in about ane in 2500 female's births worldwide(54). Females with genetic constitution XXX, on the other hand, have a normal appearance and are fertile, but endure from a mild mental handicap. Similarly, XYY males have relatively few clinical symptoms and appear phenotypically normal. They are taller than boilerplate and may show aggressive behavior and below-average intelligence. Both XXX and XYY weather condition ordinarily pass undiagnosed (iii). Determination The analysis and interpretation of these results can assuming the master causes of not-disjunction such as, the maternal age, as it elevates the risk of nondisjunction (8), meiotic errors in both phases (I and Ii) which was demonstrated in many studies(46.i °% MI, 53.9 M 2 (6) , paternal and maternal origin(90.9 % maternal and 4.5 % paternal) (4) (90.vii% maternal and five.v paternal (6) , mitotic errors (iv.5 % mitotic origin (4) three.8 % mitotic origin (6), lack of recombination(ix), exposure to toxic substances (12) and as a especial instance ; nondisjunction that affect sex chromosomes and has a major incidence in translocation carriers (Robertsonian translocation)(13). Thus the chromosomal nondisjunction doesn't accept a unique cause, it is the result of meiotic errors of paternal and maternal origin and many other factors such maternal historic period, translocations and exposure to toxic substances. At that place are differences in the frequencies and percentages of the errors incidence as shown throughout the review (11). 50 years of researches nigh aneuploid conditions, give rise to information virtually the incidence, frequency, source and the mechanisms in which nondisjunction and aneuploid condition takes place. Nowadays we consider that we accept finished the easy part, but yet have to search for the difficult one, which is the handling, prevention and avoiding the occurrence of these abnormalities, and then will it be possible? Conflicto de interés: ninguno Financiación: Universidad del Norte REFERENCES 1. Benjamin L. "Genes VIII & IX", Oxford, New. York: Oxford University Press. Goodenough U, "Genetics", Hold Saunders International. ... Genes VIII:-Benza-min L. 1st ed. 2003, Oxford University. iv. Genome:-T.A. Brown, Jhon Wiley & S. 6BT.two- BIOSTATISTICS. Unit of measurement ... [ Links ] ii. Len L, Doc. 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Fecha de aceptación: 15 de marzo de 2010
Source: http://www.scielo.org.co/scielo.php?script=sci_arttext&pid=S0120-55522010000100012
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