Down Syndrome and Turner Syndome?
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It is known that about 80% of Down Syndrome are due maternal meiotic nondisjunction, while 80% of Turner Syndrome is due paternal meiotic nondisjunction. What are the possible causes? Why is it that the "X" contributed by one specific parent gives rise to a specific Syndrome and not the other? Also, Down Syndrome is Trisomy 21, which has nothing to do with the sex chromosomes. Any help on this question is appreciated!
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Answer:
From Medical Genetics for the Modern Clinician, by Judith A. Westman: "Nondisjunction is more common in the development of eggs than in the development of sperm. Germ cells increase by mitosis prior to the birth of the individual, but the initiation of meiosis and the length of meiosis are very different in males and females. In males, cells begin meiosis after sexual maturity is reached, and replication of progenitor cells (mitosis) and meiosis continues for the lifetime of the individual, permitting men to retain fertility. In females, all cells enter meiotic prophase prior to birth and then enter a period of arrested meiosis as primordial follicles. After sexual maturity is reached, several follicles grow further with each menstrual cycle; one oocyte is ovulated each month and several die. Once all the oocytes either are ovulated or have died, a woman enters menopause. One hypothesis is that the length of time spent in arrested meiosis may contribute to the likelihood of nondisjunction; another hypothesis is that chromosomally "healthy" eggs are preferentially ovulated at earlier ages." The simple layman's translation for this quote is that the woman's eggs are more likely to contribute to nondisjunction than the man's sperm, because the eggs are very old, being made early in her life and waiting around to be ovulated. The man's sperm, by contrast, are constantly being regenerated and are never old. Therefore, the woman is generally far more likely to cause it than the man. From the UIC website: "Just as simple meiotic nondisjunction is the leading cause of autosomal chromosome abnormalities, so is nondisjunction the leading cause of the X and Y abnormalities. In autosomal abnormalities an increase in nondisjunction was associated with increasing maternal age. In sex chromosome abnormalities, one additional source of nondisjunction can be identified, the problem of X and Y pairing at first meiotic division in spermatogenesis. The X and Y have homology only in a small region (called the pseudo autosomal region) which lies near one end of each chromosome. Rather than pair along their entire length, pairing (and possible recombination) occur only in this small region. At first meiotic division in the male, pairing of X and Y looks more like end to end pairing than longitudinal pairing. This undoubtably adds to the frequency of nondisjunction." This simplified explanation is that during meiosis the chromosomes are matched up by type, and then they are separated down the middle, with one of each type going to the new daughter cell. In the mother, the match is an X chromosome against another X chromosome, which is relatively easy. In the father, the X is matched against a Y, and the two are dissimilar enough that the chance of a mismatch is greater, with both going to the same daughter cell. Hope this helps. Great question, by the way.
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Other answers
From Medical Genetics for the Modern Clinician, by Judith A. Westman: "Nondisjunction is more common in the development of eggs than in the development of sperm. Germ cells increase by mitosis prior to the birth of the individual, but the initiation of meiosis and the length of meiosis are very different in males and females. In males, cells begin meiosis after sexual maturity is reached, and replication of progenitor cells (mitosis) and meiosis continues for the lifetime of the individual, permitting men to retain fertility. In females, all cells enter meiotic prophase prior to birth and then enter a period of arrested meiosis as primordial follicles. After sexual maturity is reached, several follicles grow further with each menstrual cycle; one oocyte is ovulated each month and several die. Once all the oocytes either are ovulated or have died, a woman enters menopause. One hypothesis is that the length of time spent in arrested meiosis may contribute to the likelihood of nondisjunction; another hypothesis is that chromosomally "healthy" eggs are preferentially ovulated at earlier ages." The simple layman's translation for this quote is that the woman's eggs are more likely to contribute to nondisjunction than the man's sperm, because the eggs are very old, being made early in her life and waiting around to be ovulated. The man's sperm, by contrast, are constantly being regenerated and are never old. Therefore, the woman is generally far more likely to cause it than the man. From the UIC website: "Just as simple meiotic nondisjunction is the leading cause of autosomal chromosome abnormalities, so is nondisjunction the leading cause of the X and Y abnormalities. In autosomal abnormalities an increase in nondisjunction was associated with increasing maternal age. In sex chromosome abnormalities, one additional source of nondisjunction can be identified, the problem of X and Y pairing at first meiotic division in spermatogenesis. The X and Y have homology only in a small region (called the pseudo autosomal region) which lies near one end of each chromosome. Rather than pair along their entire length, pairing (and possible recombination) occur only in this small region. At first meiotic division in the male, pairing of X and Y looks more like end to end pairing than longitudinal pairing. This undoubtably adds to the frequency of nondisjunction." This simplified explanation is that during meiosis the chromosomes are matched up by type, and then they are separated down the middle, with one of each type going to the new daughter cell. In the mother, the match is an X chromosome against another X chromosome, which is relatively easy. In the father, the X is matched against a Y, and the two are dissimilar enough that the chance of a mismatch is greater, with both going to the same daughter cell. Hope this helps. Great question, by the way.
M
Both are genetic defects. In Turner syndrome, cells are missing all or part of an X chromosome. The condition only occurs in females. Most commonly, the female patient has only one X chromosome. Others may have two X chromosomes, but one of them is incomplete. Sometimes, a female has some cells with two X chromosomes, but other cells have only one. It started appearing in Amish due to their previous methods of interbreeding with their own. In most cases, Down syndrome occurs when there is an extra copy of chromosome 21. This form of Down syndrome is called Trisomy 21. The extra chromosome causes problems with the way the body and brain develop. It is usually associated with a woman's age. The normal separation of chromosomes in meiosis I or sister chromatids in meiosis II is termed disjunction. When the separation is not normal, it is called nondisjunction. This results in the production of gametes which have either too many or too few of a particular chromosome, and is a common mechanism for trisomy or monosomy. Nondisjunction can occur in the meiosis I or meiosis II, phases of cellular reproduction, or during mitosis. The cause of nondisjunction is unknown. Nondisjunction seems to be a chance event. Nothing that an individual does or doesn't do during their reproductive years can cause these chromosomal changes. We do know that nondisjunction occurs more frequently in the eggs of women as they get older.
CM
Both are genetic defects. In Turner syndrome, cells are missing all or part of an X chromosome. The condition only occurs in females. Most commonly, the female patient has only one X chromosome. Others may have two X chromosomes, but one of them is incomplete. Sometimes, a female has some cells with two X chromosomes, but other cells have only one. It started appearing in Amish due to their previous methods of interbreeding with their own. In most cases, Down syndrome occurs when there is an extra copy of chromosome 21. This form of Down syndrome is called Trisomy 21. The extra chromosome causes problems with the way the body and brain develop. It is usually associated with a woman's age. The normal separation of chromosomes in meiosis I or sister chromatids in meiosis II is termed disjunction. When the separation is not normal, it is called nondisjunction. This results in the production of gametes which have either too many or too few of a particular chromosome, and is a common mechanism for trisomy or monosomy. Nondisjunction can occur in the meiosis I or meiosis II, phases of cellular reproduction, or during mitosis. The cause of nondisjunction is unknown. Nondisjunction seems to be a chance event. Nothing that an individual does or doesn't do during their reproductive years can cause these chromosomal changes. We do know that nondisjunction occurs more frequently in the eggs of women as they get older.
CM
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