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37 Cards in this Set
- Front
- Back
Lyonization
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process by which all X chromosomes in excess of one are made genetically inactive and heterochromatic
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4 Key Features of X inactivation
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1) Occurs during blastocyst stage
2) It's a random process. As a result, females are a "mosaic" of maternal and paternal X chromosomes. 3) Clonal stability. Once an X is inactivated, all of the mitotic products have that same X inactivated. Thought to be achieved via particular methylation pattern 4) X Chromosome regions subject to inactivation. X-inactivation center (XIC). XIST thought to control the inactivation process - it's expressed from the inactivated chromosome!! (Some genes escape inactivation) |
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X-inactivation center/X-Inactive Specific Transcript
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Area/gene product on the "inactivated" X chromosome. Call this because several individuals who had deletions here had problems deactivating their X chromosomes.
XIST is a gene thought to control this process. It's ON THE INACTIVATED X CHROMOSOME. Some genes on the "inactivated" x chromosome actually escape the inactivation. These genes seem to have <b> homologous sequences on the Y chromosome </b>, reflecting importance of gene dosage. |
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Pseudoautosomal region
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homologous sequences of nucleotides on the X and Y chromosomes. You're getting <b> two </b> doses of these genes, and they do recombine. They undergo reciprocal exchange by crossing over and do not show strict sex-linked inheritance.
The pseudoautosomal regions get their name because any genes located within them (so far at least 29 have been found)are inherited just like any autosomal genes. So, females can inherit an allele originally present on the Y chromosome of their father and males can inherit an allele originally present on the X chromosome of their father. |
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Exceptions to X-inactivation randomness
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If a translocation occurs between X chromosome and autosome, the normal X chromosome is preferentially inactivated (thus inactivation doesn't spread to the X-autosome because that would have more serious consequences)
Has been observed in women who express disease genes located on the X chromosome. |
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Klinefelter Syndrome
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47,XXY
Tall eunuchoid habitus, intellectual develop generally ok, infertile |
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XYY
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1 in 1000 (same as Klinefelter)
Tall stature, intellectual development decent, normal fertility, no increase in children with chromosomal changes interestingly Could possibly be slightly overrepresented in prison population. Slight increase in behavior problems. |
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Turner Syndrome
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45,X
only viable human monosomy Small stature Intellectual development good, possible coarctation of aorta |
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Isochromosome
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a chromosome that has lost one of its arms and replaced it with an exact copy of the other arm. This is sometimes seen in some females with Turner syndrome
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Cytogenetic Heterogeneity: What does it mean for Turner syndrome?
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Not all ppl with Turner have monosomy X. Other kinds are isochromosome Xq, deletions of X, mosaicism, ring X chromosome (more severe developmental delay) or other anomolies
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Structural chromosome abnormality resulting in deletion of XIST gene in Turner: what happens?
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More severe phenotype, including mental retardation
Especially ring chromosome |
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Trisomy X
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47, XXX
Normal appearance, kind of tall. In the pseudoautosomal region, there may be genes regulating height (b.c Turner women are short) Normal fertility |
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Individuals having >3 sex chromosomes, eg. XXXX. What is their phenotype like?
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Tends to be more severe with both growth and mental problems present
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Sex Determination
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Processes that determine what sex an embryo will be
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Sexual Differentiation
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After Sex Determination, it's the actual cellular/morphogenetic changes that take place that distinguish one sex from another.
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Barr bodies
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An area of dark stain (heterochromatin) that is the inactivated X chromosome. Corresponds to the number of X chromosomes minus one.
(Y chromosomes are not inactivated, even if they're extra) |
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SRY genes
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Sex determining region of the Y Chromosome.
Important in sexual development. There's no homologous sequence on the X chromosome, and the gene is expression |
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Errors in the pseudosomal region: What happens?
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Genes that are typically found only on the Y chromosome could be relocated onto an X chromosome (and vice versa), resulting in 1) a male with two X chromosomes that appear normal using microscopy but contain Y-specific sequences or 2) A female with an X and a Y chromosome that appear normal using microscopy but contain no Y-specific sex determining sequences.
Example, In the presence of SRY, there will be a switch to male |
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Regions on the Y chromosome that play role in Sex Determination and Differentiation
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SRY
SOX9 DAX1:thought to interact with SRY and play role in sex differentiation cascade |
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SOX9
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Region on chromosome 17q thought to be target for SRY and is impt early factor for sex determination cascade.
Mutations of this gene result in campomelic dysplasia (large head, short trunk, bone problems). |
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Campomelic Dysplasia
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Rare, autosomal dominant condition caused by mutation of the SOC 9 gene. Results in phenotypic female with male chromosomal complement.
Large head, short trunk, bowed limbs, other bone problems. |
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Androgen insensitivity syndrome
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"Testicular feminization"
Defect in androgen receptor results in failure of response to testosterone. XY individual develops as female. Testes are present but never descend. Little pubic hair, blind vagina Gender assignment not an issue...psychosexual and sexual development are that of a normal (but infertile) female. |
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Thorough family history includes
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Biological and medical information about family members.
Info about patient's psychological experience. Info about patients' social structure and support system. |
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SCREEN for family disease
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SC - some concern
R- Reproduction; problems in pregnancy, birth defencts in family, infertility in family E - early disease, death, or disability E - Ethnicity N - Non-genetic: any other risk factors or non-medical conditions that run in the family (e.g., smoking) |
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Proband
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Affected individual coming to medical attention independently of other family members. Designated with an arrow in the pedigree.
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Characteristics of autosomal dominant
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1) Vertical transmission
2) Gene product is usually structural (non-enzymatic) protein 3) Both sexes are affected equally 4) Both sexes can transmit |
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Characteristics of autosomal recessive
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1) Horizontal inheritance
2) Both sexes affected equally 3) Both sexes equally capable of transmitting affected allele 4) Gene product is usually enzymatic protein (where half dose is enough) |
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Characteristics of X-linked recessive
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1) Males affected much more than females
2) No male-to-male transmission 3) Diagonal inheritance - affected males are related thru females in maternal line 4) No or occasional mild expression in females due to X inactivation |
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Characteristics of X-linked dominant
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Very rare
1) Twice as many females with the disorder than males (because they have 2x as many X chromosomes!) 2) No male-to-male transmission (no males pass X chr. to other males) 3) Females usually have milder expression due to X-linked inactivation 4) <b> Can distinguish between X-linked dominant and autosomal dominant by looking at female offspring of males. All will have it. </b> |
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Penetrance
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What percent of people with the mutant allele is the trait expressed at all?
E.g., Retinoblastoma: 10% are not affected. Penetrance is 90% |
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Expressivity
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The degree to which a trait is expressed. Can't talk about expressivity unless it is penetrant.
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Variable age of onset
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Variation in the time to phenotypic expression of a mutant gene.
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Pleiotropic
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Produces effects in multiple body systems
Ex. Marfan syndrome affects skeletal, cardiovascular, and ocular systems |
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Locus heterogeneity
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Mutations at two different genetic loci result in similar phenotypes (ex., several genes can result in congenital deafness because several genes control ability to hear)
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Allelic heterogeneity
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Two or more different mutant alleles at the same genetic locus
Ex., >1500 mutations have resulted in cystic fibrosis |
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Sex-limited
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Phenotype that is autosomally transmitted but expressed only in one sex. E.g., autosomal dominant male precocious puberty
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Sex-influenced
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Autosomally inherited traits that are expressed differently, in either degree or frequency, in males and females. Eg., hemochromatosis (increased iron)
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