Chromosomes and Aberrations

Chromosome & Chromosome Aberration

• Swiss botanist NAGELI first described thread-like structures in plant cell nuclei in the 1840s, calling them "transitory cytoblasts."
• Waldeyer later coined the term "chromosome" in 1888, derived from the Greek words "chromos" (color) and "soma" (body), after staining techniques improved visibility.
• Cytogenetics studies chromosome structure, properties, behavior during cell division (somatic and germ), and their influence on phenotype.
• Cytogenetics includes the study of factors causing chromosomal changes.

Chromosomes

• Chromosomes are rod-shaped, filamentous structures in the nucleus, visible during cell division.
• Chromosomes carry genes or units of heredity.
• Chromosomes become visible during cell division due to high water content in the active nucleus.
• Chromosomes are composed of thin chromatin threads called chromatin fibers.
• Chromatin fibers undergo folding, coiling, and supercoiling during prophase, becoming progressively thicker and smaller.
• Chromosomes become readily observable under a light microscope
• Chromatin fibers uncoil at the end of cell division, extending as fine chromatin threads not visible under a light microscope.

Spool-like proteins

• Chromosomes' structure keeps DNA tightly wrapped around spool-like proteins called histones.
• Without histones, DNA molecules would be too long to fit inside cells; a single human cell's DNA would stretch 6 feet if unwound.

Chromosome Discovery and Terminology

• Strausberger first described chromosomes in 1875.
• Waldeyer first used the term "chromosome" in 1888.
• Chromosomes got their name (chromo = color; soma = body) because of their marked affinity for basic dyes.
• Chromosome number is most easily counted during mitotic metaphase.

Chromosome Number & Ploidy

• Individuals of the same species typically have the same number of chromosomes.
• Closely related species often have similar chromosome numbers.
• Euploidy is the presence of a whole set of chromosomes.
• Euploidy includes conditions like haploidy, diploidy, triploidy, and tetraploidy.
• Gametes normally contain one set of chromosomes, termed haploid (n).
• Somatic cells usually contain two sets of chromosomes, termed diploid (2n).
• Polyploidy is when chromosome sets are present in multiples of "n."
• Aneuploidy is a change in chromosome number involving only a few chromosomes, not entire sets.
  • Examples include:
    • Monosomics (2n-1)
    • Trisomics (2n+1)
    • Nullisomics (2n-2)
    • Tetrasomics (2n+2)

Chromosome Number Examples

• Red viscacha rat (Tympanoctomys barrerae): 2n = 102
• Aquatic rat (Anotomys leander): 2n = 92
• Great white shark (Carcharodon carcharias): 2n = 82
• Pigeon (Columbidae): 2n = 80
• Turkey (Meleagris): 2n = 80
• African wild dog (Lycaon pictus): 2n = 78
• Chicken (Gallus gallus domesticus): 2n = 78
• Coyote (Canis latrans): 2n = 78
• Dingo (Canis lupus dingo): 2n = 78
• Dog (Canis lupus familiaris): 2n = 78 (76 autosomal, 2 sexual)
• Dove (Columbidae): 2n = 78 (based on African collared dove)
• Golden jackal (Canis aureus): 2n = 78
• Gray wolf (Canis lupus): 2n = 78
• Asiatic black bear (Ursus thibetanus): 2n = 74
• Brown bear (Ursus arctos): 2n = 74
• Polar bear (Ursus maritimus): 2n = 74
• Sloth bear (Melursus ursinus): 2n = 74
• White-tailed deer (Odocoileus virginianus): 2n = 70
• Elk (Wapiti) (Cervus canadensis): 2n = 68
• Red deer (Cervus elaphus): 2n = 68
• Horse (Equus ferus caballus): 2n = 64
• Mule: 2n = 63 (semi-infertile)
• Donkey (Equus africanus asinus): 2n = 62
• Giraffe (Giraffa camelopardalis): 2n = 62
• Bengal fox (Vulpes bengalensis): 2n = 60
• American bison (Bison bison): 2n = 60
• Cow/Bull (Bos indicus / Bos taurus): 2n = 60
• Goat (Capra aegagrus hircus): 2n = 60
• Yak (Bos mutus): 2n = 60
• Mithun (Bos frontalis): 2n = 58
• Elephant (Elephantidae): 2n = 56
• Gaur (Bos gaurus): 2n = 56
• Capuchin monkey (Cebus x): 2n = 54
• Sheep (Ovis orientalis aries): 2n = 54
• Silkworm (Bombyx mori): 2n = 54
• Spectacled bear (Tremarctos ornatus): 2n = 52
• Water buffalo (Bubalus bubalis): 2n = 50
• Swamp buffalo: 2n = 48
• Chimpanzee (Pan troglodytes): 2n = 48
• Gorilla (Gorilla): 2n = 48
• Hare (Lepus): 2n = 48
• Orangutan (Pongo x): 2n = 48
• Human (Homo sapiens): 2n = 46 (44 autosomal, 2 sex)
• Sable antelope (Hippotragus niger): 2n = 46
• Dolphin (Delphinidae Delphi): 2n = 44
• European rabbit (Oryctolagus cuniculus): 2n = 44
• Giant panda (Ailuropoda melanoleuca): 2n = 42
• Rat (Rattus norvegicus): 2n = 42
• Rhesus monkey (Macaca mulatta): 2n = 42
• Hyena (Hyaenidae): 2n = 40
• Mouse (Mus musculus): 2n = 40
• Cat (Felis silvestris catus): 2n = 38
• Lion (Panthera leo): 2n = 38
• Pig (Sus domesticus): 2n = 38
• Sea otter (Enhydra lutris): 2n = 38
• Tiger (Panthera tigris): 2n = 38
• Red panda (Ailurus fulgens): 2n = 36
• Yellow mongoose (Cynictis penicillata): 2n = 36
• Rice (Oryza sativa): 2n = 24
• Kangaroo: 2n = 16
• Koala (Phascolarctos cinereus): 2n = 16
• Pea (Pisum sativum): 2n = 14
• Fruit fly (Drosophila melanogaster): 2n = 8
• Jack jumper ant (Myrmecia pilosula): 2n = 2

Chromosome Size

• Unlike other cell organelles, chromosome size varies significantly depending on the cell division stage.
• Interphase chromosomes are longest and thinnest.
• Prophase chromosomes progressively decrease in length while increasing in thickness.
• Anaphase chromosomes are smallest.
• Metaphase chromosomes are easiest to observe and study due to their thickness, shortness, and well-spread nature in the cell.
• Chromosome measurements are generally taken during mitotic metaphase.

Chromosome Size Variation

• In mitotic phase of animal and plant species, chromosome size ranges from 0.5 to 32 μm in length and 0.2 to 3.0 μm in diameter.
• The longest metaphase chromosomes are found in Trillium (32 μm).
• Giant chromosomes in diptera can be as long as 300 μm and up to 10 μm in diameter.
• Plants generally have longer chromosomes than animals.
• Species with lower chromosome numbers tend to have longer chromosomes.
• Dicots generally have a higher number of chromosomes than monocots.
• Monocot chromosomes are longer than dicot chromosomes.

Chromosome Visualization

• Chromosomes can be distinguished by "painting" using DNA hybridization and fluorescent probes during mitosis.
• Karyotype is the general morphology of the somatic chromosome.
• Karyotypes are represented by arranging chromosomes in descending order of size with centromeres aligned.
• Idiotype represents a karyotype of a species diagrammatically, showing all morphological features; such a diagram is known as Idiotype.

Chromosome Morphology

• Chromosomes are divided into:
  • Metacentric
  • Submetacentric
  • Acrocentric
  • Telocentric

Common domestic animal chromosomes

• Cattle:
  • Bos indicus 2n=60, Largest acro submeta
  • Bostaurus 2n=60, Small meta submeta
• Buffaloes
  • River Type 2n = 50 small acro large acro, 10 submeta 38 acro
  • Swamp Type 2n = 48 " " ", 2 submeta 8 acro 36 acro
• Sheep, 2n = 54, acro acro, 6 submeta 46 acro
• Goats, 2n =60, meta submeta
• Swine, 2n =38, meta submeta, 24 submeta 12 acro
• Horse, 2n =64, acro submeta, 26 meta 36 acro
• Rabbit, 2n = 44, acro submeta, 34 submeta 8 acro

Euchromatin and Heterochromatin

• Chromosomes can be identified by regions that stain differently with various chemicals, forming chromosomal bands.
• Darker bands are generally found near centromeres or telomeres (ends); other regions stain less strongly.
• Dark-staining regions are called heterochromatic region or heterochromatin.
• Light-staining regions are called euchromatic region or euchromatin.
• Heterochromatin is classified into:
  • Constitutive - remains permanently in the heterochromatic stage.
  • Facultative - euchromatin that takes on heterochromatin characteristics during development.

Prokaryotic Chromosomes

• Prokaryotes typically have one chromosome, differing morphologically from eukaryotic chromosomes.
• Prokaryotic genome length varies considerably, bearing genes.
• RNA viruses have the smallest genome length.
• An organism with a small genome has only a few genes in its chromosome.
• A larger bacteriophage genome may have up to 150 genes.

Chromosome Banding Techniques

• G-banding: Chromosomes are treated with trypsin before staining with Giemsa to produce dark (G bands) and light bands.
• Q-banding: Chromosomes are stained with fluorescent dye (e.g., Quinacrine) that binds preferentially to AT-rich DNA.
• R-banding: Reverse of G-banding; heat denatures AT-rich DNA, and binds dyes with GC-specificity instead.
• T-banding: Identifies R bands concentrated at telomeres, using a severe heat treatment or dye combination.
• C-banding: Demonstrates constitutive heterochromatin at centromeres using denaturation with barium hydroxide before Giemsa staining.

Giant Chromosomes

• Found in certain tissues e.g., salivary glands of insect larvae, gut epithelium, Malphigian tubules, and fat bodies of some Diptera (Drosophila, Sciara, Rhyncosciara)
• Can be upto 200 times their size in the case of Drosophilia
• Chromosomes are are very long and thick.
• Often referred to as Giant chromosomes
• First discovered by Balbiani in 1881 in dipteran salivary glands, and referred to as salivary gland chromosomes
• Significance was realized after extensive studies by Painter during 1930's.
• The total length of D.melanogater giant chromosomes is about 2,000μ.
• Giant chromosomes are made up of dark staining regions, called "bands".
• They are seperated by light or non-staining regions, referred to as "interband" regions.
• Drosophila giant chromosomes, the bands are visible without staining, but become very sharp and clear after staining
• Drosophila has about 5000 bands that can be recognized.
• Some of these bands are as thick as 0.5µ, while some may be only 0.05μ thick.
• Estimates of about 25,000 base-pairs for each band now exist
• Polytene chromosome and the condition is referred to as "Polytene".
• Giant chromosome is composed of numerous strands, each strand representing one chromatid.
• Band is the condensed location of multiple strands in a chromatid

Polytene Chromosomes

• Polytene chromosomes contain numerous strands due to repeated replication of paired chromosomes without nuclear or cell division.
• The number of strands (chromatids) in a chromosome doubles after every round of DNA replication.
• Drosophila giant chromosomes have about 1,024 strands.
• Chironomous may have about 4,096 strands.
• Giant chromosome bands are formed by the stacking of chromomeres of all strands.
• Chromatin fibers are highly coiled in chromosomes and stain deeply.
• Chromatin fibers in interband regions are fully extended and take up very light stain.
• Location of Drosophila's many genes correlates with specific bands in connected chromosomes.
• Interband regions do not have functional genes.
• Specific bands and interband regions associated with them increase in diameter to form Puffs or Balbiani rings during cell developement.
• Puffs are a result of uncoiling of chromatin fibers in the chromomeres.
• Puffs are sites of active RNA synthesis.

Lampbrush Chromosomes

• Lampbrush chromosomes are named due to their similarity in appearance to brushes used to clean lamp chimneys.
• They were first observed by Flemming in 1882.
• Ruckert assigned the name lampbrush in 1892.
• Lampbrush chromosomes are found in oocytic nuclei of vertebrates (sharks, amphibians, reptiles and birds) and invertebrates (Sagitta, sepia, Ehinaster, insects).
• They are also found in plant oocytes.
• Lampbrush chromosomes reach lengths up to 800 μm, providing material for cytological studies.
• The homologous chromosomes are paired, and each is duplicated to produce two chromatids at the lampbrush stage.
• Each lampbrush chromosome features a central axial region, where the two chromatids are highly condensed.
• Each chromosome has several chromomeres distributed over its length.
• From each chromomere, a pair of loops emerges in opposite directions, vertical to the main chromosomal axis.
• One loop represents one chromatid i.e., one DNA molecule.
• Loop size may is upto an average of 9.5 µm to about 200 μm.
• The pairs of loops are from produced due to uncoiling of the two chromatin fibers present in a highly coiled state in the chromomeres.
• There is extensive RNA synthesis at the thin end of the loops, while there is little or no RNA synthesis at the thick end.
• One end of each loop is thinner (thin end) than the other end (thick end).

Chromosomal Aberrations

• Somatic (2n) and gametic (n) chromosome numbers remain constant due to precise mitotic and meiotic cell division.
• Somatic cells of a diploid species contain two copies of each chromosome (homologous chromosomes).
• Gametes contain only one copy of each chromosome or a chromosome complement/genome.
• Each chromosome in a genome contains a definite number of genes arranged in a specific sequence.
• Chromosomal aberrations are variations in chromosomal number or structure that sometimes arise due to mutation or spontaneously.
• Chromosomal aberrations are grouped into:
  • Structural
  • Numerical

Aneuploid types

• Change from the 2x state indicates Heteroploid
• One or a few chromosomes extra or missing from 2n indicate Aneuploid with symbol: 2n ± few
• One chromosome pair missing indicate Nullisomic with symbol: 2n-2
• One chromosome missing indicate Monosomic with symbol: 2n-1
• Two nonhomologous chromosomes (each chromosome from a different pair) missing indicate Double monosomic with symbol: 2n-1-1
• One chromosome extra indicate Trisomic with symbol: 2n + 1
• Two nonhomologous chromosomes (each chromosome from a different pair) extra indicate Double trisomic with symbol: 2n + 1 + 1
• One chromosome pair extra indicate Tetrasomic with symbol: 2n + 2

Euploid Types

• Number of genomes different from two indicates Euploid
• Only one genome present indicates Monoploid with Symbol: x
• Gametic chromosome number of the concerned species present indicates Haploid with Symbol: n
• More than two copies of the same genome or more than one genome present indicates Polyploid with Symbol: -
• More than two copies of the same genome present indicates Autopolyploid with Symbol: -
• Three copies of the same genome present indicates Autotriploid with Symbol: 3x
• Four copies of the same genome present indicates Autotetraploid with Symbol: 4x
• Five copies of the same genome present indicates Autopentaploid with Symbol: 5x
• Six copies of the same genome present indicates Autohexaploid with Symbol: 6x
• Eight copies of the same genome present indicates Autooctaploid with Symbol: 8x
• Two or more distinct genomes; generally each genome has two copies indicates Allopolyploid with Symbol: **
• Two distinct genomes; each has two copies indicates Allotetraploid with Symbol: (2x1 + 2x2)**
• Three distinct genomes; each has two copies indicates Allohexaploid with Symbol: (2x1 + 2x2+2x3)**
• Four distinct genomes; each has two copies indicates Alloctaploid with Symbol: (2x1 + 2x2+2x3+2x4)

Structural Chromosomal Aberrations

• Variations in chromosome structure result from chromosome breakage.
• Broken chromosomes tend to re-join at random.
• Rejoining may not be with the correct ends, leading to structural changes.
• Chromosome breakage is caused by X-rays, various chemicals, and can occur spontaneously.
• Four common types of structural aberrations:
  • Deletion
  • Duplication
  • Inversion
  • Translocation

Gene Order Examples

• A normal chromosome with genes in alphabetical order is represented as abcdefghi
• Deletion: abcghi
• Duplication: abcdefdefghi
• Inversion: abcfedghi
• translocation: abcdefxyz and uvwghi

Deletion

• Loss of a chromosome segment is known as deletion or deficiency.
• Terminal deletion occurs at the end of the chromosome.
• Interstitial or intercalary deletion is within the chromosome.
• A single break near the chromosome end can result in terminal deficiency.
• Intercalary deficiency can occurs a section may be deleted if two breaks occur.
• Deletion can produce Striking genetic and physiological effects
• Homozygous deletions are often lethal because most genes are necessary for life
• Hemizygous deletion is a normal homologue are there only being 1 copy of those genes
• Crossing over will be absent when there is a chromosome deletion
• Mutants in drosophilia can be induced, such as blonde, pale, beaded

Karyotes Deletion vs Human

• Deletions are found in prokaryotes as well, e.g., E.coli, T4 phage and Lambda phage.
• In E.coli, deletions of up to 1% of the bacterial chromosome are known.
• Chromosome deletions are usually lethal even as heterozygotes, or stillbirths
• In lambda phage, however 20% of the genome may be missing in some of the deletions

Deletion Examples and Diseases

• Prader-Willi Syndrome results from inheriting a deletion on chromosome 15 from the male parent.

  • Mental retardation, increased appetite/obesity, lack of muscle tone, short stature, small hands and feet, male hypogonadism and infertility can result.

• Cri-du-chat (Cat cry syndrome) is named as such from a cat-like cry, and is caused by deletion in the short arm of chromosome 5; cri-du-chat patients die in infancy or early childhood.

• Myelocytic leukemia- A deletion of chromosome 22, Nowell and Hungerford, called "Philadelphia" (Ph') chromosome

Duplication

• The presence of an additional chromosome segment, as compared to that normally present in a nucleus is known as Duplication.
• The location of extra is in tandem when it is where the normal segment in exactly the orientation to form tandem
• An inverted reversed tandem duplication occur when the gene sequence is in the reverse format, inverse
• In some instances, the extra is on teh displacement, is located in the same but is displaced
• A translocation is called when the additional segment is located in A non-Homologous
• Duplication means that at the end it ends up with a dificiency, while the other has a concerned.
• There have unquial consequences for small chromosome segments
• Chromosome band, an easy is produces from. X chromosome of Drosophilia and produces bae eye
• Duplication is from crossing of chromosome by from two from. X chromosome of female,

Inversion Types

• Inversion can be categoried when there is a reverse of the chromosome when oriented backwards
• This can first noticed in 1926, with with Stutevant and Plunketin
• The reverse takes place with a turn through of the 180 degrees turns by re insertion and detaches form the genes
• Breaking the broken on the broken on the close of proximmity
• May be in contact with what is not and is not supposed to.
• The parts and side with lopped loop can not and does no correspond in same way it could
• The end and in a full in an inversion

Inversion Classification

• Inversion may be classified into:
  • Pericentric - include the centromere
  • Paracentric - do not include the centromere
• In natural populations, pericentric inversions are less frequent than paracentric inversions.
• However, pericentric inversions are more common in some species such as grasshoppers.
• Paracentric inversions are frequent in natural populations, such as Drosophila

Translocation

• Integration segment is is known as translocation non-Homologous
• 1. Translocation simple,2. Translocation,3 translocation reciprocal
• Simple In this case, an integration will transpire in in the homoLogous -shift In this case an interCalay is taking placing by a integration within homoLogous drosphilia
• Reciprocity happens with 2-way Segement
• Transloation occurs more regularly

Consequences of Robertsonian fusions

• Balanced carrier (Trisomy 14) (Monosomy 14) (Monosomy 21) Trisomy 21
• Normal 14 ,14/21 Gametes
• This can occur from fertilization be a normal gamtee
• 14/21 can then have occur in possibility in. Meiosis

Chromosomal Abnormalities

• Alterations in chromosome number.
• Euploid - normal set (2n)
• Polyploidy – extra set of the entire genome.
• (3n, 4n etc)
• Aneuploidy – the number of chromosomes is not a multiple of the normal haploid number.
• Monosomy - one member of a chromosome pair is missing (2n-1)
• Trisomy - one chromosome set consists of 3 copies of a chromosome (2n+1)

Origin of Polyploidy

• Triploidy - 69XXX, 69XXY, 69XYY

  • Results from dispermy
  • Occurs by haploid sperm fertilizing diploid egg
  • Occurs 1% of the time with about a 99% mortality prior to pregnancy
  • Represents About 17% of spontenuous abortion
  • Occurs in 1 10,000 births
  • most die within one month

• Tetraploidy

  • Found in about 5% of Abortion
  • From Failure of cytokinesis
  • Often Lethal

Non-Disjunction and Causes

• Homologous chomosome that are paired from gametogensis and are ditrinbuted.

  • Unqiuallity of the Distruption.

• The non-Disjunction of chromosome separation and and are called. Are called non-disguntion

  • This can Occur in Either mitosis in embryogenses

• Mitotic not non-disjugngntion the is the. Separation it will is caused separation

  • Often occurs is. After fertilizer
  • The Cleavge will Be the Resulat

• When Miotics will occur with recive for 45 Chromossmoe, while the otehrt will 74

• Mioltics non-Dissmjustiom is is of the seperation of is called the miotic nondisjunction

• This Can occur during canmetogenesious

Chromosome Number Variation

• Euoploid when a. Complete set of chromsoom is applied to both Dipoil and haplopid

• When Aneuploty is. When. There is variation which not inclding complete Set. Chromosms

• The desicovurey of was by. Bridge, where they discovered X0 And XXY chromsosssm for. Diopsilia, which contaiend d and 9 chromsomoes, respectably, instead of 8

• Nullisomy- The pair have was of one

• Monosomy that. Singele is to be from Maz

Uses of Aneuploidy

• They have Been able to Determine how a loss have efects on chromsomoes
• Chromosoem were produced from substutuion Linens
• When alien addition and also alien substutiton lines. It has allow to to. Gene trsnafere the. Speicies
• The has enable as. Well a. Genw the is has enbaled gene

Human Trisomy: Down Syndome

• Down Syndrome: The best example of chromosne releated syndorme
• Formerly has a. Congenitial
• The discovee. Was by. Down In 1868. By. The Decsribiing common. Feature of. Disntc
• One per every 1 hase syndrome
• U.S has 250,000 Syndrome
• Costly a. is 1 blion. The

More traits of Human Syndrome

• Patients from Short Statue. Four toll. And The
• There have Been to Be the have to have. Short Handa Fimger
• They are the. Are the Mentalality.
• In human syndrome can. Have an extra chromsomoes in number 21

Trisomy Examples

• Down's Syndrome involves an extra copy of chromosome 21.
• Fluid sample that is used for the to have a mother during cell stage for observation
• Has 3 chromosoems 21, synrdome is confirmed
• About have more trisoymt after the age of 40

Trisomy birth rate and maternal age

• Incidence of birth vs materal age (years)
• The risk for mothers less than 25 years of age to have the trisomy is about 1 in 1500
  • About have more trisoymt after the age of 40
• 45,40 have in the hunder. The

Syndromes

• Chromosome Nomenclature: 47, +13 Chromosome formula: 2n+ Clinical Syndrome: Trisomy Estimated Frequency Birth: 1/20,000
• Main Phenotypic Characteristics:
• Mental deficiency and deafness, minor muscle seizures, cleft lip, cardiac anomalies
• INGR
• When some one has Dolicephaly