Molecular Genetics
XI
Mistakes
in Meiosis
As with mitosis,
non-disjunction can occur in either meiotic division..
See http://www.biology.iupui.edu/biocourses/N100/2k2humancsomaldisorders.html
Vocabulary
Using “ploidy” as our root word
euploid
means the proper number of chromosomes
aneuploid
means that the cell is missing or has gained an extra chromosome or two (NOT
SETS!)
monosomy
means that one chromosome is missing
trisomy
means that there is an extra chromosome
Non-disjunction in Meiosis I
During Anaphase I,
if the homologues do not separate properly, then one daughter cell will receive
N+1 chromosomes while the other receives N-1. In
humans, the two daughter cells resulting from a non-disjunction in anaphase I
will have not 23 duplicated chromosomes each but one with 22 (N-1) and one with
24 (N+1). After meiosis II, there will be two daughter cells with 22
chromosomes and two daughter cells with 24 chromosomes.
Non-disjunction in Meiosis II
During Anaphase II,
if the chromatids do not separate properly, then one
daughter cell will receive 24 chromosomes while the other receives 22. But the
two daughter cells that result from Meiosis I are
independent. If both come through Meiosis I normally, non-disjunction may occur
in one daughter cell but not the other. This means that a normal meiosis I
followed a non-disjunction in Meiosis II may result in half the gametes being
normal, one having N+1 chromosomes and one having N-1 chromosomes.
Take-home: non-disjunction in meiosis I is more serious than in meiosis
II
animation of non-disjunction and subsequent
fertilization:
http://www.emunix.emich.edu/~rwinning/genetics/meiosis4b.htm
Disorders resulting from
non-disjunction
Autosomal abnormalities
No human zygote can survive missing an autosome (autosomal monosomy). Zygotes with an extra chromosome (trisomy) will usually be aborted spontaneously, often before the woman suspects that she is pregnant. Three trisomies in humans do exist.
Trisomy 13 (Patau
syndrome)
It is rare for fetuses with this condition to go to term, so
it occurs in only 1 in 15,000
live births. It is rare for babies
to survive for very long if liveborn because of the multitude
of anomalies that are usually present. Forty five percent die within the first
month, 90% by six months and less than 5% reach 3 years. There is severely abnormal cerebral functions and virtually always leads to death in early infancy. This baby has very pronouced clefts of the lip and palate, broad nose, small cranium, polydactyl, deafness, and nonfunctional eyes. Heart defects and severe mental retardation are also part of the clinical picture.
http://home.earthlink.net/~heinabilene/karyotypes/trisomy13.htm
Trisomy 18 (Edwards syndrome)
Trisomy 18 is a relatively common
syndrome affecting approximately 1 out of 3,000 live births and affecting girls
more than three times as often as boys. Multiple abnormalities are associated
with the presence of an extra number 18 chromosome, many which are not
compatible with more than a few months of life. Few infants survive beyond the
first year.
Common findings include low birth weight, mental retardation, low-set ears, malformed ears, small jaw (micrognathia), hand abnormalities, congenital heart disease, hernias, and cryptorchidism. There may be many other abnormalities noted.
http://home.earthlink.net/~heinabilene/karyotypes/tri18.htm
Trisomy 21 (Down syndrome)
Trisomy 21 is an example of one form of addition in which the fetus may occasionally survive to term and beyond. Of those born with Down syndrome, 1/6 die within the first year and the average life span is 16.2 years. The non-disjunction event in meiosis that produces this anomaly increases in incidence with increasing maternal age. Trisomy 21 is one of the most common causes of mental retardation. The child can have an IQ between 25-74. An average person has an IQ between 90-110. This results in a number of characteristic features, such as short stature, broad hands, stubby fingers and toes, a wide rounded face, a large protruding tongue that makesspeech difficult. Individuals with this syndrome have a high incidence of respiratory infections, heart defects, and leukemia. The average risk of having a child with trisomy 21 is 1/750 live births. Mothers in their early twenties have a risk of 1/1,500 and women over 35 have a risk factor of1/70, which jumps top 1/25 for women 45 and over.
Down syndrome FAQs
http://www.nas.com/downsyn/faq.html
Sex chromosome abnormalities
There is more tolerance to abnormal numbers of sex
chromosomes than autosomes in humans. The
inactivation of the X chromosome and the small amount of information on the Y
chromosome may help to foster this tolerance.
Turner syndrome
There is only one case of monosomy
that may survive to birth in humans: Turner syndrome. Turner syndrome patients
are females with 44 autosomes and one X chromosome
(44, X, female). A female with Turner syndrome will NOT show a Barr body in any
of her cells since she must have one activated X in each cell. Because only one
X chromosome is present, the ovaries do not develop normally and usually do not
function fully. This means that they do not produce adequate amounts of female
hormones, so the young teenager will not go through puberty (develop breasts
and menstruate) unless these hormones are provided. Having undeveloped ovaries
also means that the woman is quite likely to be infertile, although there are
rare cases of women with Turner syndrome conceiving children.
Girls with Turner syndrome are shorter than their peers and reach an average adult height of 4 feet 8 inches, although a few women may reach or exceed 5 feet in height. Their body proportions are normal. Kidney, heart, thyroid and skeletal problems are more common in females with Turner syndrome than in the rest of the population. Mental retardation is not a feature of Turner syndrome, despite such claims in older medical textbooks.
XXX female
Occurs at a frequency of 1/1,000 female live births. No specific abnormalities are usually associated with this condition. The vast majority of women who have this condition are normal mentally and physically and are fertile. Most women with XXX who are fertile do not tend to pass the extra X to their offspring. This extra X chromosome tends to end up in a polar body after the first meiosis division. It is also possible to inherit 4 or 5 Xs. With each extra X there tends to be a corresponding increase in mental handicap, a chance of being sterile, and a lack of secondary sex characteristics.
XYY male
Jacobs Syndrome. A chromosome aberration which is caused by nondisjunction of the Y chromosome during the second phase of meiosis giving a 47 XYY karyotype. Occurence is 1/1000 live male births. Men with this karyotype are tall and have low mental ability. The high incidence of XYY males in prison compared to the normal population has led to erroneous conclusions about the effects of this syndrome.
Klinefelter’s syndrome
(XXY males)
This is Klinefelter's syndrome with a 47, XXY karyotype. A non-dysjunctional event in meiosis left two X chromosomes in an ovum. This particular anomaly is relatively common (about 1 in 500 males), with affected persons being relatively normal. Characteristics associated with this condition are tall stature and sterility. A cell from a XXY male would exhibit a Barr body.