Human Chromosomes: Morphology and Types

Human Chromosomes

• Chromosomes consist of chroma, which means color, and soma, which means body. This was defined by German anatomist Heinrich von Waldeyer-Hartz in 1888.
• Theodor Boveri and Walter Sutton independently started the study of chromosomes, their structure, and inheritance in 1903.
• Tjio and Levan determined that the correct number of human chromosomes in somatic cells is 46 (2n = 46) in 1956.

Number and Morphology of Human Chromosomes

• Metaphase human chromosomes are stretched DNA formed by two copies of sister chromatids.
• Sister chromatids are held together by a region with a highly repetitive DNA sequence, called the centromere.
• The centromere divides the chromosomes into two sections, the short arm (p) and the long arm (q).

Types of Chromosomes Based on Centromere Location

• Metacentric: Centromere is located at the center, dividing the chromosome into two arms of similar length.
• Submetacentric: Centromere is near the center, dividing the chromosome into two slightly asymmetric arms.
• Acrocentric: Primary constriction is positioned near one end of the chromosome, which produces a very short p-arm and a longer q-arm.
• Telocentric: Chromosome that only contains q-arms.

Human Chromosomes Karyotype

• Karyotype: The complete set of chromosomes of an individual.
• Humans have 46 chromosomes, divided into 23 pairs.
• Autosomes: 22 pairs are identical in both males and females.
• Sex Chromosomes: The 23rd pair, which consists of two different chromosomes termed X and Y.
• Ideograms represent the karyotype and show chromosomes' relative sizes and banding patterns.
• The tumor suppressor gene TP53 is located on the short arm of chromosome 17, band 1, sub-band 3, and sub-sub-band 1.

Autosomal Chromosomes

• There are 22 pairs of homologous chromosomes.
• Homologous chromosomes are identical, however the sequence of the genes from the maternal and paternal chromosomes can vary slightly.
• The human ABO gene has three possible alleles: IA, IB, and i.

Human Sex Chromosomes

• The Y chromosome is small, acrocentric, marked by a heterochromatic region on its long arm, with 50% of its sequence being composed of repetitive elements.
• The Y chromosome only has 63 genes that control sexual development.
• The X chromosome has over 800 genes, controls sex development and somatic characteristics, such as neuronal development.

Chromosome Abnormalities

• Numerical chromosomal abnormalities: Alterations in the number of chromosomes in the cells.
• Structural chromosomal abnormalities: Chromosome breaks and joining of the breakpoints, resulting in chromosome rearrangements.
• Chromosome alterations are found in 0.8% of liveborn infants and 25% of all miscarriages and stillbirths.

Numerical Chromosome Abnormalities - Aneuploidy

• Aneuploidy: Loss or gain of individual chromosomes.
• Polyploidy: Gain of whole sets of chromosomes.

Numerical Chromosome Abnormalities - Monosomy X (Turner Syndrome)

• Monosomy of chromosome X is the only monosomy that is compatible with life, which results in Turner syndrome and occurs in 1 in 5000 live female births.
• Most affected girls and women usually present normal intelligence, although some may present learning disabilities.

Numerical Chromosome Abnormalities - Trisomy 21 (Down Syndrome)

• Trisomy 21 is the most frequent chromosomal abnormality in humans
• It occurs in 1 in 700–800 newborns with karyotypes 47,XX or XY,+21.

Numerical Chromosome Abnormalities - Trisomy 18 (Edward Syndrome)

• Edward syndrome (Trisomy 18) is a severe genetic disorder characterized by organs abnormality and intellectual disability.

Numerical Chromosome Abnormalities - Trisomy 13 (Patau Syndrome)

• Trisomy 13 is found in about 1 in 12,000 births and results in Patau syndrome.
• The karyotype is 47,XX or XY,+13.
• It is a severe disease with a limited life expectancy, with most patients surviving for only a few days or months.

Numerical Chromosome Abnormalities - Trisomy of Sex Chromosomes

• Klinefelter syndrome (XXY): Occurs in about 1 in 1000 newborn males and can cause infertility and learning disabilities, as well as breast growth, breast cancer, and osteoporosis.
• XXX (Trisomy X or Triple X syndrome): Occurs in 1 in 1000 live female births.
• XYY karyotype (Jacobs syndrome): Occurs in 1:1000 male births.
• Tetrasomy or Pentasomy: Include karyotypes 69,XXX, 69,XXY, or 69,XYY and karyotypes 92,XXXX, or 92, XXYY.

Structural Chromosome Abnormalities

• Result from chromosome breaks followed by abnormal fusion of the breakpoints.
• Found in around 0.22% of live births.
• Can involve either only one chromosome, such as in deletions and inversions, or two or more chromosomes, such as in translocations.

Balanced vs Unbalanced Rearrangements

• Balanced rearrangements involve chromosome segments in different positions, without loss or gain of genomic material.
• Unbalanced rearrangements involve missing and/or additional genomic material.

Structural Chromosome Abnormalities - Deletions (del)

• Deletions (del) result from chromosome breakages and the loss of a chromosome segment.
• Terminal deletions include, for example, 46,XX,del(4)(p15).
• Interstitial deletions include, for example, 46,XY,del(4)(p13p15).
• Deletions can lead to monosomies, altered phenotypes, and impact viability.

Structural Chromosome Abnormalities - Duplication (dup)

• Duplication (dup) is the gain of a chromosome segment and results in partial trisomy.
• Duplications can be originated by unequal crossing over during gametogenesis or can be inherited from parents.

Structural Chromosome Abnormalities - Reciprocal Translocations

• Usually, there are no phenotypic effects for the individual.
• Unbalanced gametes with loss and/or gain may also be produced (e.g., 46,XY, der(1)t(1;11)(q32;q25).
• Can result in non-viable conceptions, miscarriages, or clinical consequences.

Structural Chromosome Abnormalities - Robertsonian Translocations

• Occur in 1 in 800 individuals in the population.
• Involve the fusion of whole arms of acrocentric chromosomes after breaks on the centromere or near the centromeric region.
• Balanced Robertsonian translocation carriers can be infertile, especially males, and are at increased risk for miscarriages.
• Robertsonian translocations gametes represent approximately 4% of patients with Down syndrome.

Structural Chromosome Abnormalities - Isochromosomes

• Isochromosomes are constituted by two copies of one chromosome arm (duplication), joined as a mirror image, with no copy (deletion) of the other arm.
• This is caused by abnormal centromere separation and breakages in both chromosome arms.
• Isochromosome of the long arm of the X chromosome is a frequent finding (about 20%) in females with Turner syndrome (46,X,i(X)(q10)).

Structural Chromosome Abnormalities - Inversions

• Inversions are intrachromosomal rearrangements that originate from two breaks in the same chromosome followed by an inverted fusion (180 degrees) of the chromosome segment.
• There are paracentric and pericentric inversions.
• Carriers of inversions may produce normal gametes, gametes with the inverted chromosome, or gametes with the two types of recombinant chromosomes.