Lecture 9 - Chromosomal abnormalities Flashcards Preview

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What are the sex chromosome aneuploidies?

Klinefelter syndrome (47, XXY), XYY male, XXX female, Turner syndrome (45, X)


Describe XXX females

1/1000 female live births, usually due to maternal meiosis 1 error, average to tall, learning deficit possible, some fertility problems


XYY males

1/1000 male live births, failure of paternal meiosis, tall, normal intelligence/fertility, clinically indistinguishable from 46,XY


Klinefelter syndrome

47, XXY - 1/1,000 male live births, 50% due to meiosis 1 error in father, tall, infertility, some female characteristics, learning deficit possible


Turner syndrome

45,X - 1/5000 live female births, short stature, short hands and fingers, normal intelligence (may have learning difficulties), webbed neck, heart problems, usually infertile - 50% of patients have 45,X, 15% have deletions of X, 10% mosaics


Do individuals with 45,X/46,XY mosaicism have male or female phenotype?

It depends! Males are usually okay. Women (Turner) - high probability of problem - gonadoblastoma


XY female

1/20,000 live births, androgen insensitivity, phenotypically normal female w/ testes, infertile - mutation of androgen receptor gene on X chromosome


XX "male"

congenital adrenal hyperplasia, autosomal recessive, overproduction of androgens in female fetus, ambiguous external genitalia, can be due to CAH in mother


XX male

1/20,000 live births, X-Y recombination near pseudoautosomal region, usually normal - if rearranged X chromosome passed to offspring could result in a turner female


Possible structural changes to chromosomes

Deletion, Duplication, Translocation, Inversion


Balanced vs Unbalanced abnormalities

Balanced - all material present but rearranged (normally clinically benign) ... Unbalanced - some of the material missing or duplicated, abnormal phenotype



loss of a part of a chromosome, leads to partial monosomy - terminal deletion (end lost) vs interstitial (internal region lost). Severity depends not as much on size of deletion but which genes and how many are missing


Wolf-Hirschhorn Syndrome

4p- deletion - microcephaly, "greek warrior helmet", require special education, increased risk for seizures



additional copy of a chromosome segment, results in partial trisomy - normally pretty rare



equal exchange involving two or more chromosomes - as long as the breaks don't occur within an important coding gene, the rearrangement should be benign - can cause shit for offspring though


Balanced translocation facts

1/500, usually phenotypically normal, translocations can be inherited, or can be de novo (karyotyping is important!)


Significance of a balanced translocation for an individual?

Increased risk another pregnancy could have unbalanced chromosome complement, increased risk of infertility or spontaneous fetal loss, increased risk of abnormal live born


Robertsonian translocation

Occur only between two acrocentric chromosomes and appear as a fusion of the long arms at the centromere - may be between nonhomologous chroms (13 and 14) or between homologous chroms (13 and 13) - results in loss of rRNA genes on chroms, but is present elsewhere = not deleterious (45 chromosomes but normal)


Risks of robertsonian translocation?

Can negatively impact meiosis resulting in nondisjunction errors (ex. child can inherit trisomy 13 by getting two normal 13s, and a 14 and 13/14)



reversal of chromosomal segment with respect to the normal gene arrangement - requires minimum of two breaks in one chromosome, often balanced but can be bad if gene interrupted


Pericentric vs Paracentric

Pericentric - The breaks occur on opposite sides of the centromere and segment - generates new chromosome with same genes in different order. May change morphology of chromosome (submetacentric to metacentric.

Paracentric - two breaks occur on same side of the centromere


Affects of paracentric inversion

Can affect fidelity of meiosis, for chromosomes to pair properly, one of the chromosomes must twist resulting in an inversion loop. Appears if inversion is suppressing recombination


Affects of pericentric inversion

Recombination within loop gives rise to recombined gametes with duplication and deletion of gene regions - however, the larger the inversion the more virable


Can more than one chromosomal abnormality occur in one person?



What is the importance of karyotype analysis?

Identify chromosomal anomalies that may be associated with disease and be able to distinguish normal variation from true abnormality