Ch. 8 Chromosome Variation

fragile x syndrome

A form of X-linked intellectual disability that appears primarily in males; results from an increase in the number of repeats of a CGG trinucleotide.

effects of inversions

An inversion may break a gene into two parts, with one part moving to a new location and destroying the function of that gene. Even when the chromosome breaks are between genes, phenotypic effects may arise from the inverted gene order in an inversion.

effects of aneuploidy

Aneuploidy usually alters the phenotype drastically. In most animals and many plants, aneuploid mutations are lethal. Because aneuploidy affects the number of gene copies but not their nucleotide sequences, the effects of aneuploidy are most likely due to abnormal gene dosage. Aneuploidy alters the dosage for some, but not all, genes, disrupting the relative concentrations of gene products and often interfering with normal development. Keep in mind that x-inactivation in mammals' sex chromosomes helps deal with aneuploidy

translocations in evolution

Apparently, a Robertsonian translocation took place in a human ancestor, creating a large metacentric chromosome from the two long arms of the ancestral acrocentric chromosomes, and a small chromosome consisting of the two short arms. The small chromosome was subsequently lost, leading to the reduced chromosome number in humans relative to that of the other apes. Translocation in Chromosome 2 in humans differs from chromosome 2 in apes, gorillas, and chimps

Familial Down Syndrome

Caused by a Robertsonian translocation in which the long arm of chromosome 21 is translocated to another chromosome (chromosome 14); tends to run in families.they have 46 chromosomes, but an extra copy of part of chromosome 21 is attached to another chromosome through a translocation. the long arm of 21 and the short arm of 14 exchange places

primary Down Syndrome

Caused by the presence of three full copies of chromosome 21 and therefore a total of 47 chromosome; arises from spontaneous nondisjunction in egg formation: about 75% of the nondisjunction events that cause Down syndrome are maternal in origin, most arising in meiosis I. .

aneuploidy

Change from the wild type in the number of chromosomes; most often an increase or decrease of one or two chromosomes. Occurs by 3 methods: 1. chromosome is lost in mitosis/meiosis due to a lack of centromere 2. robertsonian translocation--the short armed chromosome is lost 3.nondisjunction, the failure of homologous chromosomes or sister chromatids to separate in meiosis or mitosis.

dicentric chromatid

Chromatid that has two centromeres; produced when crossing over takes place within a paracentric inversion. The two centromeres of the dicentric chromatid are frequently pulled toward opposite poles in mitosis or meiosis, breaking the chromosome.

paracentric inversion

Chromosome inversion that does not include the centromere in the inverted region. (para means 'next to')

pericentric inversion

Chromosome inversion that includes the centromere in the inverted region (peri means 'around')

tandem duplication

Chromosome rearrangement in which a duplicated chromosome segment is adjacent to the original segment.

displaced duplication

Chromosome rearrangement in which the duplicated segment is some distance from the original segment, either on the same chromosome or on a different one.

autopolyploidy

Condition in which all the sets of chromsomes of a polyploid individual possessing more than two haploid sets are derived from a single species.caused by accidents of mitosis or meiosis that produce extra sets of chromosomes, all derived from a single species

mosaicism

Condition in which regions of tissue within a single individual have different chromosome constitutions.Results from nondisjunction in mitosis

allopolyploidy

Condition in which the sets of chromosomes of a polyploid individual possessing more than two haploid sets are derived from two or more species. arises from hybridization between two species; the resulting polyploid carries chromosome sets derived from two or more species.

position effect

Dependence of the expression of a gene on the gene's location in the genome.

copy-number variation

Difference among individual organisms in the number of copies of any large DNA sequence (larger than 1000 bp).include duplications and deletions that range in length from thousands of base pairs to several million base pairs. Many of these variants encompass at least one gene and may encompass several genes.

reverse duplication

Duplication of a chromosome segment in which the sequence of the duplicated segment is inverted relative to the sequence of the original segment.

psuedodominance

Expression of a normally recessive allele owing to a deletion on the homologous chromosome. normally recessive mutations on the homologous chromosome lacking the deletion may be expressed when the wild-type allele has been deleted (and is no longer present to mask the recessive allele's expression)

effects of translocations

First, they can physically link genes that were formerly located on different chromosomes.Second, the chromosomal breaks that bring about translocations may take place within a gene and disrupt its function. Third, deletions often accompany transolcations

unbalanced gametes

Gamete that has a variable number of chromosomes; some chromosomes may be missing and others may be present in more than one copy.

translocation carriers

Individual organism heterozygous for a chromosome translocation.They have 45 chromosomes. their phenotypes are normal because they have two copies of the long arms of chromosomes 14 and 21, and apparently the short arms of these chromosomes (which are lost) carry no essential genetic information. Although translocation carriers are completely healthy, they have an increased chance of producing children with Down syndrome.

uniparent disomy

Inheritance of both chromosomes of a homologous pair from a single parent. an autosomal recessive disorder could occur even if only 1 parent is a carrier

inversions in evolution

Inversions also can play important evolutionary roles by suppressing recombination among a set of genes.As we have seen, crossing over within an inversion in an individual heterozygous for a pericentric or paracentric inversion leads to unbalanced gametes and no recombinant progeny. This suppression of recombination allows particular sets of co-adapted alleles that function well together to remain intact, unshuffled by recombination.

acentric chromatid

Lacks a centromere; produced when crossing over takes place within a paracentric inversion. The acentric chromatid does not attach to a spindle fiber and does not segregate in meiosis or mitosis; so it is usually lost after one or more rounds of cell division.

nonreciprocal translocation

Movement of a chromosome segment to a nonhomologous chromosome or region without any (or with unequal) reciprocal exchange of segments.

translocations

Movement of a chromosome segment to a nonhomologous chromosome or to a region within the same chromosome.

haploinsufficient gene

Must be present in two copies for normal function. If one copy of the gene is missing, a mutant phenotype is produced.

chromosome duplication

Mutation that doubles a segment of a chromosome.

effects of chromosome duplication

Often arise from unequal crossing over. In the heterozygotes, problems arise in chromosome pairing at prophase I of meiosis because the two chromosomes are not homologous throughout their length. The pairing and synapsis of homologous regions require that one or both chromosomes loop and twist so that these regions are able to line up. The appearance of this characteristic loop structure in meiosis is one way to detect duplications. May cause changes in the phenotype

polyploidy

Possession of more than two haploid sets of chromosomes.

inversions

Rearrangement in which a segment of a chromosome has been inverted 180 degrees.For an inversion to take place, the chromosome must break in two places.

reciprocal translocation

Reciprocal exchange of segments between two nonhomologous chromosomes.a two-way exchange of segments between the chromosomes

segmental duplications

Regions larger than 1000 bp that are almost identical in sequence in eukaryotic genomes.

dicentric bridge

Structure produced when the two centromeres of a dicentric chromatid are pulled toward opposite poles, stretching the dicentric chromosome across the center of the nucleus. Eventually, the dicentric bridge breaks as the two centromeres are pulled apart.

unbalanced gene dosage

The amount of a particular protein synthesized by a cell is often directly related to the number of copies of its corresponding gene: an individual organism with three functional copies of a gene often produces 1.5 times as much of the protein encoded by that gene as that produced by an individual with two copies. Because developmental processes require the interaction of many proteins, they often depend critically on proper gene dosage. If the amount of one protein increases while the amounts of others remain constant, problems can result. Duplications can have severe consequences when the precise balance of a gene product is critical to cell function

telocentric chromosome

The centromere is at or very near the end of the chromosome

submetacentric chromosome

The centromere is displaced toward one end, creating a long arm and a short arm. (On human chromosomes, the short arm is designated by the letter p and the long arm by the letter q.)

metacentric chromosome

The centromere is located approximately in the middle, and so the chromosome has two arms of equal length.

acrocentric chromosome

The centromere is near one end, producing a long arm and a knob, or satellite, at the other end

Duplications in Evolution

The original copy can provide the essential function, whereas an extra copy from the duplication is free to undergo mutation and change. Over evolutionary time, the extra copy may acquire enough mutations to assume a new function that benefits the organism.

Robertsonian translocation

Translocation in which the long arms of two acrocentric chromosomes become joined to a common centromere, resulting in a chromosome with two long arms and usually another chromosome with two short arms. creates a metacentric chromosome with two long arms and another chromosome with two very short arms

amphidiploidy

Type of allopolyploidy in which two different diploid genomes are combined such that every chromosome has one and only one homologous partner and the genome is functionally diploid.

adjacent-1 segregation

Type of segregation that takes place in a heterozygote for a translocation. If the original, nontranslocated chromosomes are N1 and N2 and the chromosomes containing the translocated segments are T1 and T2, then adjacent-1 segregation takes place when N1 and T2 move toward one pole and T1 and N2 move toward the opposite pole.Nonviable gametes are produced

adjacent-2 segregation

Type of segregation that takes place in a heterozygote for a translocation. If the original, nontranslocated chromosomes are N1 and N2 and the chromosomes containing the translocated segments are T1 and T2, then adjacent-2 segregation takes place when N1 and T1 move toward one pole and T2 and N2 move toward the opposite pole. RARE and nonviable gametes are produced

alternate segregation

Type of segregation that takes place in a heterozygote for a translocation. If the original, nontranslocated chromosomes are N1 and N2 and the chromosomes containing the translocated segments are T1 and T2, then alternate segregation takes place when N1 and N2 move toward one pole and T1 and T2 move toward the opposite pole.

Down Syndrome

a broad, flat face, a small nose, and oval-shaped eyes. Characterized by variable degrees of intellectual disability, characteristic facial features, some retardation of growth and development, and an increased incidence of heart defects, leukemia, and other abnormalities; caused by the duplication of all or part of chromosome 21.1 in 700 human births

polyploids

any organism that has more than two sets of chromosomes (3n, 4n, 5n, or more)

karyotype

complete set of chromosomes possessed by an organism and is usually presented as a picture of metaphase chromosomes lined up in descending order of their size

fragile sites

constrictions or gaps in particular locations on a chromosome that are prone to breakage under certain conditions

cri-du-chat syndrome

due to a deletion on the short arm of chromosome 5; infants produce a cat-like cry; A child who is heterozygous for this deletion has a small head, widely spaced eyes, a round face, and is intellectually disabled.

translocations in meiosis

heterozygous for a reciprocal translocation:An individual heterozygous for this translocation would possess one normal copy of each chromosome and one translocated copy. Each of these chromosomes contains segments that are homologous to two other chromosomes. When the homologous sequences pair in prophase I of meiosis, crosslike configurations consisting of all four chromosomes form.

trisomy

is the gain of a single chromosome, represented as 2n + 1. A human trisomic zygote has 47 chromosomes. The gain of a chromosome means that there are three homologous copies of one chromosome. Most cases of Down syndrome, discussed later in this chapter, result from trisomy of chromosome 21.

tetrasomy

is the gain of two homologous chromosomes, represented as 2n + 2. A human tetrasomic zygote has 48 chromosomes. Tetrasomy is not the gain of any two extra chromosomes, but rather the gain of two homologous chromosomes, so there will be four homologous copies of a particular chromosome.

monosomy

is the loss of a single chromosome, represented as 2n − 1. A human monosomic zygote has 45 chromosomes.

aneuploidy in humans

it is prediced that 30% of miscarries are due to aneuploidy and the zygote is spontaneously aborted. Aneuploidy in humans usually produces such serious developmental problems that spontaneous abortion results. Only about 2% of all fetuses with a chromosome defect survive to birth.

rare fragile sites

sites are often associated with genetic disorders, such as intellectual disability. Most of them consist of expanding nucleotide repeats, in which the number of repeats of a set of nucleotides is increased

common fragile sites

sites are often the location of chromosome breakage and rearrangements in cancer cells, leading to chromosome deletions, translocations, and other chromosome rearrangements.

chromosome rearrangement

structure of the chromosome is altered; duplicated, deleted, or inverted;Change from the wild type in the structure of one or more chromosomes.

deletions

the loss of a chromosome segment; the normal chromosome must loop out during the pairing of homologs in prophase I of meiosis to allow the homologous regions of the two chromosomes to align and undergo synapsis.

nullisomy

the loss of both members of a homologous pair of chromosomes. It is represented as 2n − 2, where n refers to the haploid number of chromosomes. Thus, among humans, who normally possess 2n = 46 chromosomes, a nullisomic zygote has 44 chromosomes.

aneuploids

the number of chromosomes is altered: one or more individual chromosomes are added or deleted

effects of deletions

the phenotypic consequences of a deletion depend on where the deletion is located on the chromosome. If the deletion includes the centromere, the chromosome will not be able to segregate in Meiosis and the chromosome will be lost. 3 Major Consequences of Deletions: imbalanced gene dosage; pseudodominance; haploisufficient gene

autosomal aneuploidy

usually more detrimental than sex chromosome aneuploidy because autosomal cells do not have mechanisms to deal with gene dosage (such as x-inactivation) Most autosomal aneuploids are spontaneously aborted, though occasionally aneuploids of some of the small autosomes such as chromosome 21 complete development and result in a person with aneuploidy.

inversions in meiosis

when an individual is heterozygous for an inversion, the gene order of the two homologs differs, and the homologous sequences can align and pair only if the two chromosomes form an inversion loop; exhibit reduced recombination because when crossing over does take place, the outcome is abnormal gametes that result in non-viable offspring, and thus no recombinant progeny are observed. In a heterozygous individual, a single crossover within a pericentric inversion leads to abnormal gametes.