Chromosome Abnormalities in Genetics

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Questions and Answers

What year was the human chromosome number established as 46?

1959

1956 (correct)

1960

1923

Which technique requires cell culture to collect metaphase cells for analysis?

QF-PCR

Array CGH

MLPA

G-banding (correct)

Which of the following is NOT a type of chromosome abnormality?

Chromosome rearrangements

Whole chromosome aneuploidy

Gene mutation (correct)

Copy number imbalance

What condition is associated with chromosome breakage syndromes?

Ataxia telangiectasia Signup and view all the answers

Which of the following describes an outcome of whole chromosome aneuploidy?

Arises from non-disjunction during meiosis or mitosis Signup and view all the answers

Which genetic testing technique utilizes DNA instead of cultured cells?

QF-PCR Signup and view all the answers

Mosaicism can arise in an initially normal conceptus. What is an example of its numerical configuration?

47,+21/46,N Signup and view all the answers

What was established in 1959 regarding chromosomal abnormalities?

Chromosomal basis of Down syndrome Signup and view all the answers

What is the typical resolution power of G-banded chromosome analysis?

5-10 Mb Signup and view all the answers

Which of the following best describes the role of whole chromosome paints in FISH?

To investigate structurally abnormal chromosomes Signup and view all the answers

Which application of QF-PCR is focused on during prenatal cytogenetics?

Counting chromosomes for aneuploidy detection Signup and view all the answers

What does a normal copy number indicate in chromosomal analysis?

Two for each autosome and sex chromosome Signup and view all the answers

Which condition is commonly associated with segmental copy number imbalances detected by FISH?

DiGeorge syndrome Signup and view all the answers

What is the purpose of a control probe locus in FISH analysis?

To serve as a benchmark for analysis Signup and view all the answers

What is the prevalence of Robertsonian translocations?

1 in 1000 Signup and view all the answers

Which type of translocation is known to involve segments of any non-homologous chromosomes?

Reciprocal translocation Signup and view all the answers

Which reproductive risks are associated with balanced carriers of Robertsonian translocations?

Recurrent miscarriages Signup and view all the answers

In which type of chromosome inversion does the centromere lie within the inverted segment?

Pericentric inversion Signup and view all the answers

What is a common phenotype outcome for somatic mosaicism?

Likely to result in abnormal phenotype Signup and view all the answers

Which statement describes adjacent segregation in the context of translocations?

Results in unbalanced genetic content Signup and view all the answers

What type of chromosomal anomaly might occur following trisomy rescue?

Mosaicism Signup and view all the answers

What is the most common reciprocal translocation that occurs in families?

46,XX,t(11;22)(q23.3;q11.2) Signup and view all the answers

What is the primary mechanism that leads to microdeletion syndromes?

Unequal recombination at the disease locus Signup and view all the answers

Which microdeletion syndrome is associated with deletion on chromosome 22?

DiGeorge syndrome Signup and view all the answers

In array CGH, what does a red spot indicate in relation to DNA material?

Increased test material compared to control Signup and view all the answers

What type of genetic variations can array CGH detect?

Microdeletions/duplications and CNVs Signup and view all the answers

What does the presence of 'low copy repeats' facilitate in the context of chromosomal imbalances?

Gene deletion-duplication by unequal recombination Signup and view all the answers

What kind of imbalance is associated with genes of unknown function according to research studies?

Both benign and pathogenic forms of imbalance Signup and view all the answers

What is the typical size range of submicroscopic chromosomal deletions associated with microdeletion syndromes?

100 kb to 3,000 kb Signup and view all the answers

Which syndrome involves a deletion on chromosome 4?

Wolf-Hirschhorn syndrome Signup and view all the answers

Study Notes

Milestones in Genetics

1842: First observation of chromosomes in plant cells.
1850/1860: Mendelian inheritance principles established.
1880-1900: Chromosomes confirmed as vectors of heredity.
1923: Human chromosome number determined to be 48.
1953: Discovery of DNA structure by Watson, Crick, and Franklin.
1956: Tjio and Levan reported 46 chromosomes in humans.
Aneuploidy refers to an incorrect number of chromosomes.

Milestones in Medical Genetics

1959: Chromosomal basis for Down, Turner, and Klinefelter syndromes identified.
1960: Establishment of chromosomal basis for Patau and Edwards syndromes.
1962: Development of Guthrie test for genetic screening.
1969: Introduction of chromosome banding techniques.
1977: Sanger sequencing established for DNA analysis.
1983: Polymerase Chain Reaction (PCR) technique invented for DNA amplification.

Cytogenetics

Focus areas include number, structure, deletions, duplications, and chromosomal instability.

Types of Chromosome Abnormalities

Chromosome rearrangements.
Whole chromosome aneuploidy.
Copy number imbalance.

Techniques for Chromosome Investigation

Traditional Cytogenetics: G-banding, Fluorescence in situ Hybridization (FISH), breakage analysis.
Molecular Cytogenetics: QF-PCR, MLPA, Array CGH for DNA analysis.

Chromosomal Abnormalities

Chromosome Rearrangements: Linked to recurrent miscarriages and infertility.
Copy Number Imbalance: Causes dysmorphism, developmental delays, learning difficulties, and specific phenotypes (e.g., epilepsy).
Chromosome Breakage Syndromes: Includes Fanconi anemia and ataxia telangiectasia.

Whole Chromosome Aneuploidy

Caused by non-disjunction in mitosis or meiosis.
Large genomic imbalances typically result in loss of conceptions, except in cases of gene-poor chromosomes.
Trisomy 13, 18, and 21 are the only viable autosomal trisomies at live birth.

Mosaicism

Can originate from non-disjunction or anaphase lag in a normal conceptus, leading to abnormal phenotypes.
Somatic Mosaicism: May result in observable phenotypes.
Gonadal Mosaicism: Occurs during germ cell formation, often revealed through pregnancies with de novo abnormalities.

Chromosome Rearrangements

Robertsonian Translocations: Fusion of two acrocentric chromosomes (e.g., 13, 14, 15, 21, 22).
- Prevalence of 1 in 1000.
- Most common translocations: der(13;14) and der(14;21).
Reciprocal Translocations: Can occur between non-homologous chromosomes, with a prevalence of 1 in 500.
- Usually unique to families except for one recurrent variant: 46,XX,t(11;22)(q23.3;q11.2).
Inversions: Includes pericentric (involving the centromere) and paracentric (not involving the centromere) inversions.

Investigation Techniques

G-Banding: Provides a resolution of ~5-10Mb.
Fluorescence In Situ Hybridization (FISH): Uses fluorescent markers to detect specific DNA sequences; critical for structural chromosome analysis.

Prenatal Cytogenetics

Traditional methods (G-banding) require ~2 weeks for results; FISH and QF-PCR provide faster results for pregnancy management.

Segmental Copy Number Imbalance

Normal copy number for most chromosomes is 2, except for sex chromosomes.
Deletions and duplications can manifest as microdeletion syndromes, which recur due to genomic predispositions.

Microdeletion Syndromes

Recognizable syndromes include DiGeorge (del(22q)), Prader-Willi (del(15q)), Williams (del(7q)), and Angelman (del(15q)).
Caused by submicroscopic chromosomal deletions due to unequal recombination.

Array Comparative Genomic Hybridization (Array CGH)

Detects whole chromosome aneuploidy, microdeletions/duplications, subtelomere imbalances, and copy number variants.
Studies show that normal individuals may carry multiple small copy number variations (CNVs), contributing to phenotypic variations.

Clinical Implications

Identifying unreported imbalances can be complex, as genes involved may not correlate directly with the presenting clinical features or indications for referral.

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Description

Explore the key milestones in genetics and medical genetics related to chromosome abnormalities and genomic rearrangements. This quiz covers historical discoveries from the observation of chromosomes to the establishment of human chromosome numbers and their significance in genetic disorders.