Medical Genetics Wk 3 Flashcards
What is the only natural mechanism of reproduction in diploid eukaryotes
Sexual reproduction
What does successful fertilisation depend on
some form of sexual differentiation in the reproductive organisms.
Dissimilar, or heteromorphic, chromosomes, such as the XY pair in mammals, characterize one sex or the other in a wide range of species, resulting in their label as sex chromosomes.
What serves as the underlying basis of sex determination
Genes rather than chromosomes
All the cells that contribute to one’s body are… with the exception of
Somatic cells
Gametes (the germ line)
What does a genome contain
in the nucleus of human somatic cells consists of 46 chromosomes, made up of 24 different types and arranged in 23 pairs
What are the 22 pairs described as
22 are alike in males and females and are called autosomes, originally numbered in order of their apparent size from the largest to the smallest.
What does the remaining pair comprise of
two different types of sex chromosomes: an X and a Y chromosome in males and two X chromosomes in females. In females, the sex chromosomes, the two X chromosomes, are likewise largely indistinguishable.
In males,however, the sex chromosomes differ. One is an X, identical to the Xs of the female, inherited by
a male from his mother and transmitted to his
daughters; the other, the Y chromosome, is
inherited from his father and transmitted to his
sons.
What is G banding
Is a technique used in cytogenetics to produce a visible karyotype by staining condensed chromosomes. It is useful for identifying genetic diseases.
Who demonstrated that 46 was indeed a human diploid number
Joe Hin Tijio and Albert in 1956
Describe the size of the Y chromosome
It is smaller than the X chromosome but it also contains few genes
X has 1000 genes while Y has fewer than 200 and most of them are inactive
What is Klinefelter syndrome
Around 1940, scientists identified two human abnormalities characterized by aberrant sexual development, Klinefelter syndrome (47,XXY) and Turner syndrome (45,X).
Description of Klinefelter syndrome
Are generally tall;
➢Have long arms and legs, large hands and feet.
➢Usually have genitalia and internal ducts that are male, but their testes are rudimentary and fail to produce sperm. At the same time, feminine sexual development is not entirely suppressed. ➢Slight enlargement of the breasts (gynecomastia) is common;
➢The hips are often rounded.
➢This ambiguous sexual development, referred to as intersexuality, can lead to abnormal social development.
➢ Intelligence is often below the normal range as well.
Describe how Klinefelter syndrome occurs
occurs in about 1 of every 660 male births and is the most common sex chromosome disorder in males
The karyotypes 48,XXXY, 48,XXYY, 49,XXXXY, and 49,XXXYY are similar phenotypically to 47,XXY, but manifestations are often more severe in individuals with a greater number of X chromosomes.
Recent studies have also shown that the variability in phenotypes for men with a 47,XXY genotype is correlated with copy number variations (CNVs), particularly duplications, on the X chromosomes.
What are the cases most often
Most often they have an XXY complement in addition to 44 autosomes, which is why people with this karyotype are designated 47,XXY.
What is Turner syndrome
the affected individual has female external genitalia and internal ducts, but the ovaries are rudimentary.
What are other characteristic abnormalities
Short stature (usually under 5 feet),
➢ Skin flaps on the back of the neck,
➢ Underdeveloped breasts.
➢ A broad, shieldlike chest sometimes Intelligence is usually normal
Why does Turner syndrome occur
Either the sperm was missing an X or Y chromosome or the egg was missing the X chromosome and the sperm carried the Y chromosome
The baby is always female
Symptoms:
- infertility
-Early menopause
- learning disabilities
Why does Turner syndrome occur
Can result from karyotypes other than 45,X including individuals called mosaics whose somatic cells display two different genetic cell lines, each exhibiting a different karyotype
What are the most common combinations
Such cell lines result from a mitotic error during early development, the most common chromosome combinations being 45,X / 46,XY and 45,X / 46,XX.
Thus, an embryo that began life with a normal karyotype can give rise to an individual whose cells show a mixture of karyotypes and who exhibits varying aspects of this syndrome.
What are most cases for people with Turner syndrome
most often have only 45 chromosomes, including just a single X chromosome; thus, they are designated 45,X.
What have scientists determined about both these syndromes
that the Y chromosome determines maleness in humans. In its absence, the person’s sex is female, even if only a single X chromosome is present. The presence of the Y chromosome in the individual with Klinefelter syndrome is sufficient to determine maleness, even though male development is not complete.
Similarly, in the absence of a Y chromosome, as in the case of individuals with Turner syndrome, no masculinization occurs.
What is important to note about the absence of X chromosome
we cannot conclude anything regarding sex determination under circumstances where a Y chromosome is present without an X because Y-containing human embryos lacking an X chromosome (designated 45,Y) do not survive.
What is 47,XXX syndrome
The abnormal presence of three X chromosomes along with a normal set of autosomes (47,XXX) results in female differentiation.
The highly variable syndrome that accompanies
this genotype, often called triplo-X, occurs in about
1 of 1000 female births. Frequently, 47,XXX women are perfectly normal and may remain unaware of their abnormality in chromosome number unless a karyotype is done.
What happens in other cases
➢Underdeveloped secondary sex characteristics, ➢Sterility ,
➢Delayed development of language and motor skills, and
➢Mental retardation may occur.
➢Those affected are often taller than average.
What the complications of 47,XXX syndrome
Learning difficulties
Decreased muscle tone
Seizures
Kidney problems
What are rare instances
48,XXXX (tetra-X) and 49,XXXXX (penta-X) karyotypes have been reported. The syndromes associated with these karyotypes are more pronounced than 47,XXX
the presence of additional X chromosomes appears to disrupt the delicate balance of genetic information essential to normal female development
What is 47,XYY condition or Jacobs syndrome
These males were significantly above average in height and had been incarcerated as a result of dangerous, violent, or criminal propensities. Of the nine males studied, seven were of subnormal intelligence, and all suffered personality disorders.
Symptoms in a baby who has XYY syndrome can include:
hypotonia (weak muscle tone)
➢delayed motor skill development, such as with walking or crawling
➢delayed or difficult speech
Symptoms in young child or teenager can include:
an autism diagnosis
➢attention difficulties
➢delayed motor skill development, such as with writing
➢delayed or difficult speech
➢emotional or behavioral issues
➢hand trembling or involuntary muscle movements ➢hypotonia (weak muscle tone)
➢learning disabilities
➢taller-than-average height
In adults, infertility is a possible symptom of XYY syndrome.
What are the interrelated steps of sex determination
Establishment of chromosomal sex (i.e., XY or XX) at the time of fertilization
• Initiation of alternate pathways to differentiation of one or the other gonadal sex, as determined normally by the presence or absence of the testis- determining gene on the Y chromosome
• Continuation of sex-specific differentiation of internal and external sexual organs
• Especially after puberty, development of distinctive secondary sexual characteristics to create the corresponding phenotypic sex, as a male or female.
What has the human genome project suggested
The Y chromosome has at least 75 genes, compared to 900-1400 genes in X
What are pseudoautosomal regions
present on both ends of the Y chromosome and share homology with regions on the X chromosome and synapse and recombine with it during meiosis
What are male specific region of the Y (MSY)
does not synapse or recombine with the X chromosome /about 95 percent of Y chromosome/.
Equal euchromatic /containing functional genes/ and heterochromatic regions /lacking genes/.
What is sex determining region (SRY)
a critical gene that controls male sexual development /Within euchromatin, adjacent to the PAR of the short arm of the Y chromosome/. At six to eight weeks of development, the SRY gene becomes active in XY embryos. SRY encodes a protein that causes the undifferentiated gonadal tissue of the embryo to form testes.
The protein is called Testis determining factor (TDF)
What are disorders of sex development (DSDs)
DAZ gene- a member of the DAZ gene family and is a candidate for the human Y chromosomal azoosperima factor (AZF)
What is azoospermia
Is the medical condition of a man whose semen contains no sperm
Describe the Y chromosome in sex determination
The prevalence of Y chromosome deletions and microdeletions in the general male population is reported to be approximately 1 in 2000 to 3000 males
How many males are infertile
Approx 2% of otherwise healthy males are infertile because of severe defects in sperm production, and it appears likely that de novo deletions or mutations of genes on Yq account for a significant proportion of these.
Therefore what happens…
Thus men with idiopathic infertility should be karyotyped, and Y chromosome molecular testing and genetic counseling may be appropriate before the initiation of assisted reproduction by intracytoplasmic
sperm injection for such couples, mostly
because of the risk for passing a Yq microdeletion responsible for infertility to the infertile couple’s sons.
What is SRY is the major testis determining gene
X and Y chromosomes normally recombine within the Xp/Yp pseudoautosomal segment in male meiosis. If recombination occurs below the pseudoautosomal boundary, between the X- specific and Y-specific portions of the chromosomes, sequences responsible for male gonadal sex determination
(including the SRY gene) may be translocated from the Y to the X
What is testicular DSD
Fertilization by a sperm containing such an X chromosome leads to a phenotypic male with XX testicular DSD. In contrast, fertilization by a sperm containing a Y chromosome that has lost SRY will lead to a phenotypic female with XY complete gonadal dysgenesis.
