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What is a Barr body
Inactive X chromosome in a female somatic cell, or the inactive Z in a male. It is not condensed, and therefore can be detected in a swab without culturing the cells
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Lyonization
All extra X chromosomes in a female is inactivated and packed into heterochomatin causing mosaic traits
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In Interphase chromosomes are not
Condensed
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Chromosome parts are named how
 - The ends are the telomeres
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Chromosomes are for karyotyping are obtained from a cell in mitosis because
They are condensed in metaphase
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Steps to obtaining chromosomes for karyotyping
- 1. Obtain a blood sample
- 2. Grow the cells in a growth medium with PhytoHemAgglutinin (lymphocytes will start division)
- 3. Add colchicine to block division in metaphase
- 4. Few hours later, harvest cells, add fixative and hypotone liquid
- 5. Let one drop fall onto a slide (When the drop hits, the cell membrane bursts, and the chromosomes will spread a short distance)
- 6. Banding pattern is obtained through one of several chemical/enzymatic treatments
- 7. Analyzing the result normally starts with ordering the chromosomes
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What are some sources for obtaining cells for karyotyping in adults
- – Blood (leukocytes): culture 2-3 days
- – Bone marrow biopsy: no culture
- – Fibroblast cells: culture 2-3 weeks
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What are some sources for obtaining cells for karyotyping in Prenatals
Amniotic cells: culture 2-3 weeks (can be performed around week 16
Chorionic villus sample: culture not necessary, but separation from maternally derived tissue is necessary (This can be done around week 11)
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Karyotyping
Ordered display of all chromosomes from one cell
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How are karyotyped cells ordered
According to size and position of centromere
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Acrocentric chromosome are
A chromosome with its centromere located quite near one end of the chromosome. This is where the RNA genes are located (five pairs)
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Metacentric
A chromosome having its centromere in the middle
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Chromosome is said to be submetacentric
If arms' lengths are unequal
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The earlier in the cell cycle you harvest chromosomes
The less condensed they are
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G-banding is a technique for visible karyotyping and contains chromosomes that have
- Fewer transcriptionally active genes
- More condensed chromatin structure
- Higher in A-T basepairs
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Heterochromatin is a
Chromosomal region that is not transcriptionally active
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Constitutive (useful) heterochromatin is mostly around
Centromeres, & near telomeres (<6% of total DNA)
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Heterochromatin is condensed when
even in interphase!
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What kind of genes do Heterochromatin often have
- Repeat areas
- Genes not needed in a specific cell type
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Polyploidy:
3 (rarely 4) copies of all chromosomes; not viable; 3 copies = triploid
One of most common reasons for early pregnancy loss
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Trisomy
Excess of one chromosome
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What is the most common trisomy but not compatible with life
Trisomy 16, common cause of miscarriages
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In trisomy which pairs are compatible with life
Only trisomy of 13, 18, 21, or X,Y
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Monosomy
- Lack of one chromosome
- Only monosomy X is compatible with life
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In trisomy 21 how many actually survive to birth
80% of conceptions die in utero
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Monosomy is only viable with X chromosome, what is the chance of it surviving
More than 99% of these die in utero
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What is an inversion
The chromosomes were flipped
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When counting bands on the chromosome, which direction do you count
From the centromere out
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The Types of Structural Abnormalities in chromosomes are
- • Deletion (del)
- • Inversion (inv)
- • Duplication (dup)
- • Insertion (ins)
- • Ring (r) (Lost telomeres at both end)
- • Translocation, reciprocal (t)
- • Translocation, Robertsonian (der) or (rob)
- • Isochromosome (iso)
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Ring Chromosome Formation
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Translocations have two types
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Results of Reciprocal Translocations
- The unbalanced version affects multiple genes
- Common: Mental retardation and heart defects
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Downs Syndrome
Diagnostic signs include mental retardation and specific shapes of the head and often hand and feet
Complications: 40 % have heart malformations
Hypothyroidism
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Causes of Downs Syndrome
Most often an error in segregating the chromosomes in the first maternal meiosis
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Mosaicism is caused by
Non-disjunction in mitosis, therefore it happens after the zygote formation
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Ageing of Down Syndrome Patient often exhibits
- Early senility
- Alzheimer’s disease
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What is thought to be the reason for Alzheimer’s disease in trisomy 21
The APP gene is on chromosome 21 and presumably overexpressed when three copies are present
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What are the only chromosome numbers in trisomy that can be compatible with life
13, 18, and 21 or X,Y
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Multiple cases in a family of Downs syndrome is Likely due to
Robertsonian translocation in the family
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Master control (SRY) is
Sex-determining gene on the Y chromosome
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Presence of SRY (master control gene) will in most cases lead to
A male gonad; without SRY, the gonad stays female
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True Hermaphrodites are caused by what two possibilities
Prenatal exposure to progesterone or androgen
Inherited deficiency of 11- or 21-hydroxylase in adrenal cortex
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Adrenogenital Syndrome
- Hyperplasia of adrenal cortex
- Early detection is critical in females
- In males, penile enlargement rarely detected Premature puberty in toddlers
- Treatment with cortisol, surgical reconstruction when needed
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Androgen Insensitivity Syndrome
46, XY Externally and psychosexually female; no uterus and fallopian duct, no Wolffian ducts, non-descended testes in abdomen
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5α-reductase type 2 deficiency (Male Intersex (B))
- Partial feminization at birth (variable), testes often non-descended.
- Many of these raised as females until puberty
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Indications for Karyotyping should be used in what cases
- Suspicion of recognized syndrome
- Unexplained mental retardation
- Unexplained congenital malformations
- Pregnancy loss/infertility
- Abnormality in sexual development
- Malignancies
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Pleitropy
One gene that influences many phenotypes negative or positively
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Locus Heterogeneity
Many different genes can cause the same genetic issue
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Allelic Heterogeneity
Different mutations at the same locus cause the same disorder
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Balanced reciprical translocation
An equal exchange of chromosome arms between two sets of chromosomes. (harmless) but can cause miscarriages in women with it in their genome
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The Acrocentric chromosomes are
13, 14, 15, 21, and 22
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Robertsonian translocation is
Translocations involving the acrocentric chromosomes
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