7/29/2019 Cytogen

1/11

Chromosome Terminology

chromosome number generally a constant for a specieshaploid the number of chromosomes found in a gamete (n)diploid the number of chromosomes found in a zygote (2n)

chromosome size relative length is one way to classify chromosomes within aspecies

chromosome homologues members of a chromosome pair, found in the

diploid statetelomere the termination of the linear chromosome, marked by long,repetitive sequences

centromere a constriction along a chromosome with specific repetitivesequences, which organize its kinetochore.kinetochore a protein structure which attaches a chromosome to thespindle fibers during cellular division

chromosome morphology another way to classify chromosomes within aspecies using specific stains during periods of cellular divisionmetacentric describing chromosomes with centrally located centromeresacrocentric describing chromosomes with centromeres towards one endtelocentric describing chromosomes with terminally located centromeres

7/29/2019 Cytogen

2/11

Cytogenetics

Cytogenetics is the study ofcells at the chromosomal level.

Chomosomes have historicallybeen studied by microscopicanalysis during mitoticmetaphase.

Banding of the chromatin isrevealed using the Giemsastaining complex.

Images of the chromosomesare sorted in a chart to formwhat is known as a karyotype.

7/29/2019 Cytogen

3/11

Polyploidies Polyploidy is the state of a nucleus having three or more sets of the

genome. In organisms that can tolerate polyploidy, even-numbered ploidies

are fertile, and odd-numbered are not. Tetraploid yeasts, fish, and amphibia have all been observed in

nature and may represent increased potential for evolution. Endopolyploidy is polyploidy of a specific tissue within a diploid

organism. The human liver, for example, will contain tetraploid andoctoploid cells.

Polyploidy in plants is common. They are usually more robust and larger than their diploid counterparts.

Triploid and pentaploid crops produce seedless varieties of fruit and canbe cultivated vegetatively.

An alloploid individual contains the genomes of two or more relatedspecies.

Autopolyploidy refers to an increase in the number of chromosomesets within a species.

7/29/2019 Cytogen

4/11

Human Triploidy

Individuals with threecopies of eachchromosome are triploid.

Triploidy accounts for17% of all spontaneousabortions and 3% ofstillbirths.

Causes: Two spermatozoa fertilize

one oocyte. A haploid spermatozoon

fertilizes an oocyte thatundergoes a completenondisjunction ofchromosomes.

7/29/2019 Cytogen

5/11

Classes of Aneuploidy

abnormality description

monosomy one missing chromosome

trisomy one extra chromosome

deletion portion of a chromosome missingduplication portion of a chromosome present twice

inversion portion of a chromosome reversed in direction

translocation portions of two chromosomes exchanged

Autosomal monosomies and trisomies are deleterious due toimbalance in relative gene dosages.

Duplications are generally less harmful than deletions. Inversions and translocations are often associated with position

effects.

7/29/2019 Cytogen

6/11

Nondisjunctionin meiosis I Anaphase INondisjunctionin meiosis I

Anaphase II

Nondisjunctionin meiosis II

Gametes

Abnormal gametes Abnormal gametes Normal gametes

Partial Meiotic Nondisjunctions

7/29/2019 Cytogen

7/11

Mosaic Aneuploidy

When an aneuploid gamete is fertilized by a normalgamete, an aneuploid zygote is produced.

Partial nondisjunctions can also occur during mitosis,

resulting in a somatic mutation and mosaicism. A mosaic can also be produced from a trisomic zygote if

an extra chromosome is lost in mitosis duringdevelopment, correcting the aneuploidy for that cellsprogeny.

Mosaic Down Syndrome, for example, has far morevariability in symptoms than typical Down Syndrome,depending on what portions of the body are affected.

7/29/2019 Cytogen

8/11

Autosomal Monosomies and Trisomies

Most autosomal monosomies and trisomiesare inviable.

Trisomies of some of the smaller autosomes

can survive birth but will manifest syndromicdisorders. Trisomy 13 (Patau Syndrome), ~1/20,000 births, less than 20% live

past first month. Symptoms include mental retardation,microcephaly, seizures, and cyclopia.

Trisomy 18 (Edward Syndrome), ~1/8,000 births, less than 50%

live past first month. Symptoms include mental deficiencies,micrognathia, heart and kidney abnormalities.

Trisomy 21 (Down Syndrome), ~1/800 births, over 85% live pastfirst year. Symptoms include retardation of mental development,social skills, and physical growth, facial abnormalities such asflattened nose and epicanthal folds.

7/29/2019 Cytogen

9/11

Alterations in Sex Chromosome

Number Sex chromosomal aberrations are better tolerated due to

the small size of the Y and a natural mechanism forcorrecting relative gene dosage for the X Lyonizationor X-chromosome inactivation. Triple-X syndrome: Occurring in 1:2000 live births, these

females may be asymptomatic but some may have tall stature,learning disabilities, delayed motor coordination, and infertility.

Turner syndrome (XO): Occurring in 1:2000 live births, thesefemales may show short stature, webbed neck, and infertility.

Klinefelter syndrome (XXY): Occurring in 1:2000 live births,these males may be asymptomatic but some may have tallstature, feminized body shapes, and infertility.

Jacob syndrome (XYY): Occurring in 1:2000 live births, thesemales are usually asymptomatic but some may have tall statureand learning disabilities.

7/29/2019 Cytogen

10/11

Other Chromosome Aberrations

Misaligned or unequal crossover events lead todeletions and duplications.

Crossover events between non-homologouschromosomes leads to translocation.

Crossover events within a chromatid results ininversions.

7/29/2019 Cytogen

11/11

Evolution by Gene Duplication Genes can be duplicated by anumber of mechanisms:

genome duplication(tetraploidy)

chromosome duplication(tetrasomy)

mobile element expansion(retrotransposition) unequal crossing over

Unequal crossover results intandem gene duplication.

Over the course of many

generations, replicated genesaccumulate mutations andevolve into paralogues.

Paralogues are genes within aspecies sharing a commonancestral gene, and togetherthey form a gene family.