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You are watching: During _____ sister chromatids separate.

StatPearls . Sweetheart Island (FL): StatPearls Publishing; 2021 Jan-.


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Genetics, Nondisjunction

Samantha F. Gottlieb; Connor Tupper; Connor C. Kerndt; David H. Tegay.

Author Information

Introduction

The human body is made up of trillions that somatic cells with the capacity to division into similar daughter cells facilitating organismal growth, repair, and an answer to the changing environment. This process is dubbed “mitosis.” In gamete production, a different type of cell department occurs referred to as “meiosis.” The outcome of meiosis is the development of 4 daughter cells, either sperm or egg cells, v reduction division which outcomes in a haploid match of chromosomes in every gamete. At fertilization, the haploid sperm cabinet nucleus merges with the haploid egg cabinet nucleus, which restores the diploid chromosomal complement and also confirms the development of the zygote. Throughout anaphase the the cabinet cycle, chromosomes are separated to opposite ends of the cell to create two daughter cells. Nondisjunction is the failure of the chromosomes come separate, which produces daughter cells v abnormal numbers of chromosomes. <1><2><3>


Cellular

The genome is encoded by the chemical sequence the DNA nucleotides in ~ our cells. In durations of cabinet growth, histone proteins approximately DNA room acetylated bring about less interaction between the DNA and also histone protein. This opened up DNA is dubbed euchromatin and allows transcriptional enzymes accessibility to the DNA. Before periods of cell division, the histone proteins are deacetylated permitting for the formation of a condensed kind of DNA dubbed heterochromatin. Somatic human being cells contain 23 paired chromosomes or 46 total chromosomes. Forty-six is taken into consideration the “diploid” number (2n), when 23 is considered the “haploid” number (1n) or fifty percent the diploid number. “Aneuploidy” describes the presence of one abnormal number of chromosomes. Monosomy (n-1) is a kind of aneuploidy identified by lacking a solitary chromosome leading to 45 full chromosomes. Trisomy (n+1) is another type of aneuploidy that has an extra chromosome causing 47 full chromosomes. Each form of aneuploidy have the right to be attributed to nondisjunction throughout mitosis or meiosis. <4><5><6>


Mechanism

There are 2 parts to the cabinet cycle: interphase and also mitosis/meiosis. Interphase have the right to be further subdivided into growth 1 (G1), synthesis (S), and growth 2 (G2). Throughout the G phases, the cell grows by creating various proteins, and during the S phase, the DNA is replicated so the each chromosome includes 2 the same sister chromatids.

Mitosis consists of 4 phases: prophase, metaphase, anaphase, and telophase. In prophase, the atom envelope breaks down and chromatin condenses. In metaphase, the chromosomes line up along the metaphase plate, and also microtubules affix to the kinetochores of each chromosome. In anaphase, the chromatids separate and also are pulled by the microtubules to opposite ends of the cell. Finally, in telophase, the nuclear envelopes reappear, the chromosomes unwind right into chromatin, and also the cell undergoes cytokinesis, i m sorry splits the cell right into 2 identical daughter cells.

Meiosis goes through all 4 phases the mitosis twice, with modified mechanisms the ultimately create haploid cells instead of diploid. One alteration is in meiosis I. Homologous chromosomes are separated rather of sister chromatids, developing haploid cells. That is during this procedure where we watch crossing over and independent assortment leading to the increased genetic diversity of the progeny. Meiosis II progresses the same way as mitosis, yet with the haploid variety of chromosomes, ultimately producing 4 daughter cells all genetically unique from the original cell.

Nondisjunction have the right to occur throughout anaphase that mitosis, meiosis I, or meiosis II. Throughout anaphase, sister chromatids (or homologous chromosomes because that meiosis I), will certainly separate and also move to opposite poles that the cell, pulled by microtubules. In nondisjunction, the separation stops working to happen causing both sisters chromatids or homologous chromosomes to be traction to one pole that the cell.

Mitotic nondisjunction can occur due come the inactivation of one of two people topoisomerase II, condensin, or separase. This will an outcome in 2 aneuploid daughter cells, one with 47 chromosomes (2n+1) and the various other with 45 chromosomes (2n-1).

Nondisjunction in meiosis I occurs when the tetrads fail to separate during anaphase I. In ~ the end of meiosis I, there will certainly be 2 haploid daughter cells, one with n+1 and the various other with n-1. Both of these daughter cells will certainly then walk on to division once an ext in meiosis II, creating 4 daughter cells, 2 with n+1 and also 2 through n-1.

Nondisjunction in meiosis II results from the failure of the sisters chromatids to separate throughout anaphase II. Since meiosis ns proceeded without error, 2 of the 4 daughter cells will have actually a normal match of 23 chromosomes. The other 2 daughter cells will certainly be aneuploid, one through n+1 and also the various other with n-1. 


Testing

In-utero, diagnosis the fetal chromosomal aneuploidy can be made through performing cytogenetic analysis of fetal cells, typically obtained with amniocentesis or chorionic villus sampling. The fetal chromosomal enhance is analyzed through performing a karyotype test, counting the chromosomes, and analyzing under irradiate microscopy, all while in search of abnormalities in chromosomal number or structure. Countless prenatal screening test exist to help administer an age-adjusted danger of fetal chromosomal aneuploidy through analysis of miscellaneous markers or cell-free fetal DNA in maternal serum. <7><8>

With in vitro fertilization (IVF), trial and error can also be performed before implantation through preimplantation hereditary diagnosis (PGD), polar human body diagnosis (PBD), or blastomere biopsy. PGD is a method used to recognize normal embryos that will be implanted right into the mother, though technologically demanding and also with added expense compared to prenatal diagnosis. PBD deserve to detect maternally acquired aneuploidies and is reasonably quick to do when compared to PGD. Lastly, a blastomere biopsy deserve to be obtained prior to implantation for hereditary analysis. However, blastomere biopsy locations the arising embryo at greater risk and therefore is not at this time a recommended typical of practice.


Clinical Significance

Mitotic nondisjunction can reason somatic mosaicism, through the chromosome imbalance just reflected in the direct offspring the the initial cell wherein the nondisjunction occurred. This can cause some forms of cancer, consisting of retinoblastoma.

Meiotic nondisjunction is of greater clinical significance because most aneuploidies room incompatible v life. However, some will an outcome in viable offspring through a spectrum the developmental disorders.

Autosomal Trisomies

Patau syndrome: Trisomy of chromosome 13


Clinical Features: Rocker-bottom feet, microphthalmia (abnormally little eyes), microcephaly (abnormally little head), polydactyly, holoprosencephaly, slot lip and palate, congenital love disease, and severe intellectual disability. Life expectations is seldom longer than one year.
Clinical Features: Rocker-bottom feet, low set ears, micrognathia (abnormally little jaw), clenched hands v overlapping fingers, congenital love disease, and severe intellectual disability. Life expectations is normally less than one year.
Clinical Features: single palmar crease, level facies, prominent epicanthal folds, duodenal atresia, congenital love disease, Hirschsprung disease, intellectual disability. Notably raised risk to construct Alzheimer"s condition or leukemia. Life expectations is about 60 years.
Clinical Features: Tall, lengthy extremities, gynecomastia, mrs hair distribution, testicular atrophy, developmental delay.
X chromosomes room inactivated together Barr bodies. Therefore, 2 extra Barr bodies room seen, though no clinical abnormalities result.

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Clinical Features: Unusually brief stature, shield chest, congenital heart disease, webbed neck, horseshoe kidney, ovarian dysgenesis.