Chromosomal Abnormalities Lecture Review

Flashcards covering chromosome classification, banding techniques, FISH, numerical and structural chromosomal abnormalities, and specific syndromes like Down, Edwards, Patau, Klinefelter, Turner, Cri du Chat, Wolf-Hirschhorn, Angelman, Prader-Willi, Williams, DiGeorge, and WAGR syndromes, along with definitions of mosaicism and chimerism.

How are chromosomes classified based on centromere position?

They are classified as metacentric, acrocentric, or submetacentric.

What is a metacentric chromosome?

A chromosome with its centromere positioned near the middle, making its two arms almost equal in length.

What is an acrocentric chromosome?

A chromosome with its centromere placed very close to one end, resulting in one very long arm and one very short arm.

What is a submetacentric chromosome?

A chromosome with its centromere in an intermediate position, making one arm slightly longer than the other.

What is the primary purpose of staining chromosomes?

To show unique banding patterns that help detect deletions, duplications, and structural abnormalities.

Which banding method is mainly used to detect and study structural and numerical chromosome abnormalities in clinical diagnosis?

Giemsa banding (G-banding).

Which banding method uses heat and highlights chromosome ends with a reversed pattern?

R-banding.

What does C-banding stain?

The heterochromatin near the centromere.

What is the benefit of high-resolution banding?

Done in prophase or prometaphase, it shows more bands and allows detection of small abnormalities like microdeletions.

What does 15q12 signify in chromosome notation?

Band 12 on the long arm (q) of chromosome 15.

What is Fluorescent In-situ Hybridization (FISH)?

A technique that uses fluorescent DNA probes on patient chromosomes to detect deletions, duplications, extra copies, and chromosomal rearrangements.

What are the three main categories of chromosomal abnormalities?

Numerical, Structural, and Mixoploidy.

What is a euploid cell?

A cell with a multiple of 23 chromosomes (e.g., haploid gametes and diploid somatic cells).

What is polyploidy?

When a cell has an extra complete set of chromosomes, such as triploidy (69,XXX) or tetraploidy (92,XXXX) in humans.

What can cause triploidy?

A diploid sperm or egg, or fertilization by two sperm (dispermy).

What is aneuploidy?

When a cell has gained or lost one or more chromosomes.

What is the main cause of autosomal aneuploidies?

Nondisjunction during meiosis I or II.

What is the difference between monosomy and trisomy?

Monosomy is only one copy of a chromosome, while trisomy is three copies.

What is mosaicism?

A condition where nondisjunction in early mitosis of a zygote creates two or more different cell lines within the same individual.

What is the chromosomal cause of Down Syndrome?

Trisomy 21 (an extra copy of chromosome 21).

What are some characteristic facial features of Down Syndrome?

Depressed nasal root, upslanting palpebral fissures, small/overfolded ears, and a flat maxilla and malar region.

Which gene's overexpression is associated with learning and memory defects in Down Syndrome?

DYRK1A.

What is the chromosomal cause of Edwards Syndrome?

Trisomy 18 (an extra copy of chromosome 18), often noted as 47,XY,+18.

What is a characteristic limb anomaly in Edwards Syndrome?

Clenched fist with overlapping fingers.

What is the chromosomal cause of Patau Syndrome?

Trisomy 13 (an extra copy of chromosome 13), often noted as 47,XY,+13.

What are some craniofacial abnormalities associated with Patau Syndrome?

Cleft lip/palate, microphthalmia, iris coloboma, microcephaly, and holoprosencephaly.

What is Klinefelter Syndrome?

A condition in males with an extra X chromosome (47,XXY instead of 46,XY).

What are some key features of Klinefelter Syndrome?

Small testes, low testosterone, infertility, tall stature, long arms/legs, less body hair/muscle, and sometimes gynecomastia.

What is Turner Syndrome?

A condition in females missing all or part of one X chromosome (45,X).

What are some characteristic features of Turner Syndrome?

Short stature, webbed neck, broad 'shield' chest, streak ovaries leading to infertility and delayed puberty, and heart defects like bicuspid aortic valve or coarctation of the aorta.

What is a Robertsonian Translocation?

The fusion of two acrocentric chromosomes (13, 14, 15, 21, 22) at the centromere, with the loss of their short arms.

How can a Robertsonian Translocation lead to Familial Down Syndrome?

If chromosome 21 is involved in the fusion (e.g., t(14;21)), a carrier may be healthy, but can pass on extra chromosome 21 material to a child, causing Down Syndrome.

What is the cause of Male XX Syndrome (46,XX male) in most cases?

Translocation of the SRY gene from the Y chromosome onto an X chromosome.

What are the features of Female XY Syndrome (Swyer syndrome)?

Normal female appearance with a uterus and fallopian tubes, but streak gonads (nonfunctional ovaries), leading to no normal puberty and infertility.

What is the cause of Cri du Chat Syndrome?

A deletion on the short arm of chromosome 5 (5p− syndrome).

What is a key diagnostic sign of Cri du Chat Syndrome in infancy?

A high-pitched, cat-like cry.

What is the cause of Wolf–Hirschhorn Syndrome?

A terminal deletion of the short arm of chromosome 4 (4p−).

What is a distinctive facial feature of Wolf–Hirschhorn Syndrome?

A 'Greek warrior helmet' face, characterized by a broad flat nasal bridge and high forehead.

What is the genetic cause of Angelman Syndrome?

Loss or inactivation of the maternal chromosome 15 (15q11-q13, UBE3A gene).

What are some key features of Angelman Syndrome?

Developmental delay, severe intellectual disability, speech impairment, ataxia, seizures, and microcephaly.

What is the genetic cause of Prader–Willi Syndrome?

Loss or inactivation of the paternal chromosome 15 (15q11-q13).

What is a hallmark behavioral issue in Prader–Willi Syndrome?

Hyperphagia, leading to insatiable appetite and obesity from childhood.

What is the cause of Williams Syndrome?

A small deletion on chromosome 7q11, including genes like ELN (elastin) and LIMK1.

What are some key features of Williams Syndrome?

An 'elfin' facial appearance, a very friendly and outgoing personality, learning disabilities (especially visual-spatial), and heart defects like supravalvular aortic stenosis.

What is the cause of DiGeorge Syndrome?

A small deletion on chromosome 22q11.2, often due to recombination between repeated DNA sequences, affecting genes like TBX1.

What are the common clinical features associated with DiGeorge Syndrome?

Heart defects (conotruncal anomalies), thymic hypoplasia (weak immune system), parathyroid hypoplasia (hypocalcemia), and cleft palate.

What biological process underlies the various defects seen in DiGeorge Syndrome?

Defective neural crest cell migration during development.

What is the cause of WAGR Syndrome?

A small deletion on chromosome 11p13, involving genes like WT1 and PAX6.

What do the letters in WAGR Syndrome stand for?

W: Wilms tumor, A: Aniridia, G: Genitourinary abnormalities, R: Retardation (growth & developmental delay).

What is the definition of mosaicism?

An individual having two or more genetically distinct cell lines that originate from the same zygote, typically due to a mutation or nondisjunction after fertilization.

What is the definition of chimerism?

An individual having two or more genetically distinct cell lines that originate from different zygotes, usually from the fusion of two embryos or blood/marrow transfer between twins.