Ch 8: Variation in Chromosome Structure and Number

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Natural variation & Karyotypes

Natural variation

We look at chromosomes in actively dividing cells (188)

Cytogeneticists have figured out 3 features for classifying and identifying chromosomes: centromere location, size, and banding pattern (188).

Centromere location: The centromere is never exactly at the center, so each chromosome has a short arm (p) and long arm (q).

Metacentric: Centromere is near the middle.

Submetacentric: Centromere is slightly off center.

Acrocentric: Centromere is significantly off center, but not at the end.

Telocentric: Centromere is at one end of chromosome. The shirt arm may be nearly nonexistent.

A karyotype is a micrograph in which all the chromosomes within a single cell have been arranged in a standard fashion (188).

Arranged with short arms on top, large arms on bottom.

Numbered according to size, with largest chromosomes having smallest numbers (so chromosomes are numbered 1-22).

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Unnatural variation

Deletions, Duplications, Inversions, and Translocations

Deletions and duplications are changes in the total amount of genetic material with a single chromosome (188).

When a deletion occurs, a segment of chromosome material is missing (189).

The affected chromosome is deficient in a significant amount of genetic material

Deficiency also describes a missing region of chromosome.

When a duplication occurs, a section of a chromosome is repeated compared to the normal parent chromosome (189).

Inversions and translocations move around chromosomes (189).

An inversion involves a change in the direction of the genetic material along a single chromosome (189).

A translocation occurs when one segment of a chromosome becomes attached to a different chromosome or to a different part of the same chromosome (190).

A simple translocation occurs when a single piece of chromosome is attached to another chromosome.

A reciprocal translocation occurs when 2 different types of chromosomes exchange pieces. 2 abnormal chromosomes are produced.

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Deletions and Duplications

Deletions are bad, mmkay?

A deletion occurs when a chromosome breaks in 1 or more places and when a fragment of the chromosome is lost. The entire process produces a chromosome with a terminal deletion (190).

The piece without the centromere is the one that's lost and degraded.

When a chromosome has broken in 2 places to produce 3 chromosomal fragments, the central fragment is lost and the 2 outer pieces reattach to each other. This creates an interstitial deletion (190).

Deletions can also occur when recombination takes place at incorrect locations between 2 homologous chromosomes (190).

1 chromosome has has a deletion and 1 chromosome has a duplication.

Phenotypic consequences depend of the size of the deletion and if it involves vital genes (190).

When deletions have a phenotypic effect, they are usually detrimental (190).

Larger deletions tend to be more harmful because more genes are missing (190-191).

Duplications might be okay though

Duplications will result in extra genetic material (191)

Sometimes chromosomes will cross over at non-homologous sites, This results in 1 chromatid with an internal duplication and another chromatid with a deletion (191).

The chromosome with the extra genetic material carries a gene duplication because the number of copies of gene C has been increased to 2.

The phenotypic consequences of duplications tend to be correlated with size.

In general, small duplications are less likely to have harmful effects than are deletions of a comparable size (191).

Duplications may lead to gene families

Most duplications will not have a phenotypic effect, but they're still important because they provide raw material for the addition of more genes into a species' chromosomes (191-192)

This may lead to the formation of a gene family, 2 or more genes that are similar to each other.

When 2 or more genes are derived from a single ancesteral gene, the genes are homologs. Homologs within a single species are called paralogs. They constitute a gene family (192).

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Inversions

Inversions and their Consequences

A chromosome with an inversion contains a segments that has been flipped to the opposite direction (big surprise). They are classified according to the location of the centromere (195).

Pericentric inversion: Centromere lies within the inverted region of the chromosome.

Paracentric inversion: Centromere is found outside the inverted region.

Because the total amount of genetic material remains the same,the majority of inversions do not have a phenotypic consequence (195).

Sometimes, however, it will have a consequence. If either of the breakpoints in the chromosome is in a vital gene, the function of the gene is disrupted, producing a phenotypic effect.

In other cases, an inversion may reposition a gene on a chromosome in a way that alters its normal level of expression. This is a position effect, meaning that a change in phenotype occurs when the position of a gene changes from one chromosomal site to a different location.

Inversion Heterozygotes and Crossing over

An individual that carries one copy of a normal chromosome and one copy of an inverted chromosome is known as an inversion heterzygote (196).

They might be phenotypically normal, but they have a high probability of producing haploid cells that are abnormal in their total genetic content.

The cause of the abnormality is r/t crossing over within the inverted region. Pairs of normal homologous sister chromatids synapse in meiosis I, but in order for that to happen, an inversion loop must form. This permits the homolgous genes on both chromosomes to align next to each other (196).

If a crossover occurs within this loop, highly abnormal chromosomes are produced.

Consequences of crossover depend on whether inversion is pericentric or paracentric. In pericentric crossovers where the crossover is in the inverted area, only 2 of the 4 sister chromatids crosses over. This yields 2 abnormal chromosomes (197)

Both chromosomes have a segment that is deleted and a segment that is duplicated.

These abnormal chromosomes can result in inviable gametes. Or they can be passed to offspring, where they produce phenotypic abnormalities.

In paracentric inversion crossovers, a dicentric chromosome that contains 2 centromeres and an acentric fragment that contains no centromere are both produced(197).

The acentric fragment is lost and degraded in subsequent cell divisions.

The dicentric bridge is the region of the chromosome connecting the 2 centromeres. If the centromeres try to move toward opposite poles during anaphase, the dicentric bridge will be forced to break at a random location.

The result of this crossover is 1 normal chromosome, 1 inverted chromosome, and 2 chromosomes with deletions.

The chromosomes with deletions result from breakage of dicentric chromosomes. They are the missing genes that were located on the acentric fragment.

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Translocations

What a translocation is

Eukaryotic cells have evolved telomeres, which tend to prevent translocations from occurring. They allow cells to distinguish where a chromosome ends and prevent the attachment of chromosomal DNA to the natural ends of a chromosome (197).

Mechanism #1 of getting translocations: If cells are exposed to things that cause chromosomes to break, the broken ends lack telomeres, become reactive, and bind to another chromosome that is also reactive. DNA repair enzymes will usually recognize these reactive ends and join them back together.

If multiple chromosomes are broke, the reactive ends can be joined incorrectly to produce abnormalities.

Mechanism #2 of getting translocations: Abnormal crossovers. A reciprocal translocation can be produced when 2 nonhomologous chromosomes cross over. This is rare (198).

Reciprocal translocations are also called balanced translocations. They usually occur with no phenotypic consequence because genetic material isn't lost (198).

Their offspring, however, is at risk of getting an unbalanced translocation. In these translocations, significant portions of genetic material are duplicated and/or deleted.

These ones have phenotypic consequences. They can even cause death.

They can occur because some of the chromosomes do not segregate evenly.

A Robertsonian translocation arises from breaks near the centromeres of 2 nonhomologous acrocentric chromosomes (199).

Most common type in humans.

Only involves the acrocentric chromosomes 13, 14, 15 21, and 22.

Reciprocal translocations and segregation of chromosomes

Whether or not people with balanced translocations produce gametes with unbalanced chromosomes depends on segregation in meiosis I (199).

A translocation cross can occur when the homologous chromosomes attempt to synapse with each other, but form an unusual structure because of the translocations (199).

For translocated chromosomes, the expected segregation pattern is governed by the centromeres (199).

Each haploid should receive one centromere located on chromosomes 1 and 2. This can occur 1 of 2 ways.

Alternate segregation:

Following meiosis II, 4 haploid cells are produced. 2 are normal, 2 have reciprocal (balanced) translocations.

One daughter cell receives 2 normal chromosomes, and the other cell gets to translocated chromosomes.

Alternate segregation is a process in which the chromosomes diagonal to each other within the translocation cross sort into the same cell.

Adjacent-1 segregation:

Adjacent chromosomes segregate into the same cell

After anaphase of meiosis I, each daughter receives 1 normal and 1 translocated.

After meiosis II is completed, 4 haploid cells are produced. All of them are genetically imbalanced because part of 1 chromosome has been deleted and another has been duplicated.

If these abnormal gametes unite with a normal gamete, the zygote is expected to be abnormal genetically and probably phenotypically.

Adjacent-2 segregation can occur. In this case, centromeres do no not segregate as they should. 1 daughter receives both copies of the centromere on chromosome 1; in the other, both copies are on chromosome 2 (200).

4 abnormal haploid cells that are unbalanced are made.

This is very rare.

In many cases, the haploids from adjacent-1 segregation are not viable, lowering fertility. This condition is called semisterility (200).

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8.2: Variation in Chromosome Number

Variation can be in the number of sets of chromosomes and/or variations in the number of particular chromosomes within a set (201).

Euploids have a chromosome number that is an exact multiple of the chromosome set (201).

Triploids have 3 sets of chromosomes.

Polyploids have 3 or more sets of chromosomes.

Geneticists use "n" to represent a set of chromosomes. Diploids are 2n, triploids are 3n, and tetraploids are 4n (201).

Chromosome number can also vary by aneuploidy, which involves an alteration in the number of particular chromosomes so that the total number of chromosomes is not an exact multiple of a set (201).

Animals that are trisomic have 1 extra chromosome for 1 chromosome pair rather than receiving an entire extra set of chromosomes for everything. They are 2n+1.

Animals that are lacking a single chromosome would be monosomic. They are 2n-1.

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Aneuploidy

Aneuploidy often causes a detrimental imbalance in gene expression

Aneuploidy commonly causes an abnormal phenotype. This is because the gene is overexpressed (in cases of trisomy) or underexpressed (in cases on monsomy) (201-202).

The imbalance among many genes appear to underlie the abnormal phenotype effects that aneuploidy will cause (202).

Aneuploidy in human causes abnormal phenotypes

In most cases, abnormal embryos do not develop properly and result in spontaneous abortion (202).

Most of known trisomies occur in chromosomes that are relatively small (13, 18, 21), and thus may carry fewer genes than larger chromosomes (202).

Trisomies of other human autosomes are believed to be lethal. In addition, monosomies in all automsomes are presumed to be lethal (202).

Variation in the number of X chromosomes, however, is a different story. These are usually not lethal, possibly due to X inactivation. Individuals with additional X chromosomes will have the extras converted into Barr bodies in the somatic cells (202).

The correct level of mammalian gene expression results from 2 copies of each autosome and 1 copy of each X-linked gene (203).

When X-linked genes do have a phenotypic effect, it may be due to expression of X-linked genes prior to embryonic X inactivation or to the expression of genes on the inactivated X chromosome (203).

Older parents are more likely to produce children with abnormalities in chromosome number (203).

Down syndrome is most commonly caused by nondisjunction (204).

More specifically, nondisjunction of chromosome 21 during meiosis I in the oocyte.

The connection between maternal age and down syndrome may be due to the age of the oocyte.

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Variations in euploidy

Variations occur naturally in some species

Polyploidy in mammals is generally lethal. However, in haplodiploid species, one of the sexes is haploid and the other is diploid (204).

Variations in certain tissues

Diploids will sometime produce polyploid tissues. An example is the liver in humans.

Occurrence of polyploid tissues or cells in diploid organisms is known as endopolyploidy (205).

Increase in chromosome number in certain cells may enhance ability to produce specific gene products.

A polytene chromosome is a bundle of chromosomes that lie together in a parallel fashion. This results from repeated rounds of chromosomal replication. These are found in the salivary glands of Dorsophila and some other insects.

Different b/c replicated chromosomes remain attached to each other,

Homologous chromosomes synapse and replicate; during process they aggregate to form a single structure w/several polytene arms.

Central point where chromosomes aggregate is called the chromocenter. Each of 4 types of chromosomes is attached here near its centromere.

Polytene chromosomes are large enough to be seen during interphase, unlike normal chromosomes (205-206).

Polytene chromosomes have a characteristic banding pattern; each dark band is known as a chromomere (206).

Patterns are much more detailed than those observed in metaphase chromosomes.

Polytene chromosomes have allowed geneticists to study organization and function of interphase chromosomes in great deal (206).

Variations are common in plants

Polyploidy will display some outstanding agricultural characteristics (206).

Polyploids with an odd number of chromosome sets (such as triploids and pentaploids) are usually steile b/c they produce highly aneuploid gametes (206).

Unequal separation of homologous chromosomes during anaphase of meiosis I b/c an odd number cannot e divided equally between 2 daughter cells (207).

Sterility can result in a seedless fruit, such as domestic bananas and seedless watermelons (207).

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Meiotic & Mitotic Nondisjunction

Meiotic nondisjunction can produce aneuploidy or polyploidy

Can occur during anaphase of meiosis I or II (207).

During meiosis I, an entire bivalent migrates to one pole. After completion,, 4 resulting haploids are abnormal.

During meiosis II, 2 abnormal and 2 normal haploids are made (207-208).

A complete nondisjunction is when all of the chromosomes undergo nondisjunction and migrate to 1 of the daughter cells (208).

Result is 1 diploid and 1 cell with no chromosomes.

Cell with no chromosomes is not viable, but the diploid may participate in fertilization to produce a triploid,

Can result in polyploid organisms.

Mitotic nondisjunction can produce a patch of tissue

Abnormalities in chromosome number occurring after fertilization will happen during mitosis (208).

A couple ways this could happen (208):

Sister chromatids may separate improperly.

The sister chromatids separate during anaphase, but one of the chromosomes is improperly attached to a spindle so it would not migrate to a pole.

Condition in which a subset of cells are genetically different from rest of organism is called mosaicism (208).

Size and location of mosaic depends on timing and location of original abnormality (208).

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Autopolyploidy, Alloploidy, and Allopolyploidy

Autopolyploidy, alloploidy, and allopolyploidy

An individual with one or more extra sets of chromosomes is called an autopolyploid (209).

Alloploidy results from interspecies crosses; this results in changes in chromosome number (209).

An alloploid w/one set of chromosomes from different species is called an allodiploid. This is more likely to occur between close evolutionary relatives.

An allopolyploid contains 2 or more sets of chromosomes from 2 ore more species (209).

An allotetraploid contains 2 complete sets of chromosomes from 2 different species.

Allotetraploids will usually arise from allodiploids, but it can occur when a somatic cell in an allodiploid undergoes complete nondisjunction (209).

Allodiploids are often sterile, but allotetraoloids are not

An important determinant of success in producing fertile allodiploids is the degree of similarity between the species (209).

Evolutionarily related chromosomes from 2 different species are called HOMEOlogous chromosomes. These allodiploids are fertile because the homeologous chromosomes can properly synapse (209-210).