Chromosomal Mutations Chapter 8

Chapter Overview 8.1 Specific Terminology 8.2 Variation in # of Chromosomes Results from Nondisjunction 8.3 Monosomy May Have Severe Phenotypic Effects 8.4 Trisomy Involves Addition of a Chromosome to a Diploid Genome 8.5 Polyploidy Is Prevalent in Plants 8.6 Variation Occurs in the Structure & Arrangement of Chromosomes 8.7 – 8.10 Deletions, Duplications, Inversions, & Translocations 8.11 Fragile Sites Are Susceptible to Chromosome Breakage

Terminology Chromosomal aberrations vs. mutations Most diploid species normally contain precisely two haploid chromosome sets Many known variations: change in the total number of chromosomes deletion or duplication of genes or segments of a chromosome rearrangements of the genetic material either within or among chromosomes

Terminology Aneuploidy Euploidy gain or loss of one or more chromosomes has other than an exact multiple of the haploid set Monosomy, Trisomy, etc. Euploidy Complete haploid sets are present Polyploidy - more than two sets of chromosomes are present (common in plants)

Table 8-1 Copyright © 2006 Pearson Prentice Hall, Inc. Table 8.1 Terminology for Variation in Chromosome Numbers Table 8-1 Copyright © 2006 Pearson Prentice Hall, Inc.

Nondisjunction Chromosomal variation can arise from nondisjunction Chromosomes or chromatids fail to disjoin and move to opposite poles during meiosis I or II Trisomy 21 (Down Syndrome) is an example of an aberration caused by nondisjunction

Figure 8-1 Copyright © 2006 Pearson Prentice Hall, Inc. Figure 8-1 Nondisjunction during the first and second meiotic divisions. In both cases, some of the gametes formed either contain two members of a specific chromosome or lack that chromosome. Following fertilization by a gamete with a normal haploid content, monosomic, disomic (normal), or trisomic zygotes are produced. Figure 8-1 Copyright © 2006 Pearson Prentice Hall, Inc.

Monosomy The loss of a single chromosome (monosomy) can have severe genotypic & phenotypic effects What sex disorder is an example of a monosomy? TURNER SYNDROME (XO) Monosomies of autosomes usually lethal in animals/humans

Partial Monosomy Partial Monosomy (segmental deletion) only a section of a chromosome is lost Cri-du-chat syndrome A small part of the short arm of chromosome 5 is lost Mentally retardation (variable) Small head w/ unusual facial features Cry - mewing of a distressed cat

Figure 8-2 Copyright © 2006 Pearson Prentice Hall, Inc. Figure 8-2 A representative karyotype and photograph of a child exhibiting cri-du-chat syndrome (46,5p). In the karyotype, the arrow identifies the absence of a small part of the short arm of one member of the chromosome 5 homologs. Figure 8-2 Copyright © 2006 Pearson Prentice Hall, Inc.

Cri-du-chat

Trisomy Trisomy – addition of a chromosome to a diploid genome Trisomies in sex chromosomes Less dramatic phenotype than trisomies for autosomes, which are often lethal Examples? XXX XYY Klinefelter’s (XXY)

Trisomy 3 copies of one chromosome are present, so pairing configurations are usually irregular At any particular region along the chromosome length, only 2 of the 3 homologs may synapse, though different regions of the trio may be paired

Trivalents Trivalent - three copies of a chromosome are synapsed In some cases, prior to the first meiotic division, one bivalent and one univalent may be present instead of a trivalent

Down Syndrome Down syndrome results from trisomy of chromosome 21 Down syndrome has 12 to 14 characteristics, and affected individuals express 6 to 8 on average 1 in 700 children in the U.S. Mother’s age a factor Familial DS - a translocation of chromosome 21 (rarer)

Figure 8-5 Copyright © 2006 Pearson Prentice Hall, Inc. Figure 8-5 The karyotype and a photograph of a child with Down syndrome. In the karyotype, three members of the G-group chromosome 21 are present, creating the 47, condition. Figure 8-5 Copyright © 2006 Pearson Prentice Hall, Inc.

Maternal Age Down syndrome is usually a result of nondisjunction of the maternal chromosome 21 during meiosis Incidence as maternal age

Maternal Age How could the age of a mother relate to rate of nondisjunction? Possible Theory: Human females undergo primary oogenesis (Meiosis I) as fetuses Oocyte development is stopped at that stage until puberty Each primary oocyte undergoes Meiosis II during monthly ovulation throughout life Therefore, an older woman has ova that have been arrested for 10 – 20 years longer than her earlier ova Currently, no DIRECT evidence to support Genetic counseling, amniocentesis, CVS (chorionic villus sampling)

Other trisomies Patau syndrome (trisomy 13) Edwards syndrome (trisomy 18)

Patau Syndrome Fatal (2-3 months or at birth) 1/19,000 live births

Edwards Syndrome Fatal (2-3 months) 1/8000 live births 80% females

Trisomy vs. Monosomy Trisomies are found in aborted fetuses at a much higher rate than monosomies (monosomies generally never found) Why do trisomies show a higher rate of survival? Monosomy of a chromosome may reveal a recessive (lethal) Early development a delicate process – may require equal amts of gene products

Polyploidy Polyploidy – more than 2 haploid sets of chromosomes (prevalent in plants) Naming of polyploids is based on the number of sets of chromosomes found: Triploid - 3n Tetraploid - 4n Pentaploid - 5n, etc.

Animals Lower order animals Flatworms, leeches, brine shrimp (parthogenesis) Goldfish, salmon, salamanders Argentian rodent (tetraploid) Polyploids more normal (pheno) than aneuploids WHY?

Plants Triploid crops: banana, apple, ginger Tetraploid crops: durum or macaroni wheat, maize, cotton, potato, cabbage, leek, tobacco, peanut Hexaploid crops: chrysanthemum, bread wheat, oat Octaploid crops: strawberry, dahlia, pansies, sugar cane

Polyploidy – how? Two scenarios can give rise to polyploid organisms Autopolyploidy Allopolyploidy Autopolyploidy - the addition of one or more sets of chromosomes identical to the haploid complement of the same species (nondisjunction, double fert., no div after replication) Allopolyploidy - the combination of chromosome sets from different species as a consequence of interspecific matings

Figure 8-9 Copyright © 2006 Pearson Prentice Hall, Inc. Figure 8-9 Contrasting chromosome origins of an autopolyploid with an allopolyploid karyotype. Figure 8-9 Copyright © 2006 Pearson Prentice Hall, Inc.

Endopolyploidy Endopolyploidy - only certain cells in an otherwise diploid organism are polyploid. In these cells, replication and segregation of chromosomes occur without nuclear division

Chromosomal Variation Variations in a chromosome can occur in one (or more) of the following ways: Deletions Duplications Inversions Nonreciprocal translocations Reciprocal translocations

Figure 8-14 Copyright © 2006 Pearson Prentice Hall, Inc. Figure 8-14 Overview of the five different types of rearrangement of chromosome segments. Figure 8-14 Copyright © 2006 Pearson Prentice Hall, Inc.

Deletions Deletion: missing region of a chromosome When a chromosome breaks in one or more places and a portion of it is lost, the missing piece is referred to as a deletion (or a deficiency) Terminal deletion – deletion occurs near one end of the chromosome Intercalary deletion – deletion occurs in the interior of the chromosome

Figure 8-14a Copyright © 2006 Pearson Prentice Hall, Inc. Figure 8-14a Overview of the five different types of rearrangement of chromosome segments. Figure 8-14a Copyright © 2006 Pearson Prentice Hall, Inc.

Pairing (Synapsis) of ID When one chromosome undergoes an intercalary deletion, this presents problems for synapsis with its homolog The unpaired region of the normal homolog must loop out of the linear structure into a deletion or compensation loop

Figure 8-15 Copyright © 2006 Pearson Prentice Hall, Inc. Figure 8-15 Origins of (a) a terminal and (b) intercalary deletion. In part (c), pairing occurs between a normal chromosome and one with an intercalary deletion by looping out the undeleted portion to form a deletion (or a compensation) loop. Figure 8-15 Copyright © 2006 Pearson Prentice Hall, Inc.

Prader – Willi & Angelman Deletion of specific segment of chromosome 15 Prader-Willi syndrome - mental retardation, obesity, short stature, unusually small hands & feet Inherited from father Angelman syndrome - spontaneous laughter, jerky movements, & other motor/mental symptoms Inherited from mother

Duplications Duplication - fragment becomes attached as an extra segment to a sister chromatid Arise as the result of unequal crossing over during meiosis or through a replication error prior to meiosis

Figure 8-14b Copyright © 2006 Pearson Prentice Hall, Inc. Figure 8-14b Overview of the five different types of rearrangement of chromosome segments. Figure 8-14b Copyright © 2006 Pearson Prentice Hall, Inc.

Figure 8-17 Copyright © 2006 Pearson Prentice Hall, Inc. Figure 8-17 The origin of duplicated and deficient regions of chromosomes as a result of unequal crossing over. The tetrad at the left is mispaired during synapsis. A single crossover between chromatids 2 and 3 results in deficient and duplicated chromosomal regions. (See chromosomes 2 and 3, respectively, on the right.) The two chromosomes uninvolved in the crossover event remain normal in their gene sequence and content. Figure 8-17 Copyright © 2006 Pearson Prentice Hall, Inc.

RNA Genes Many organisms have multiple copies of the ribosomal RNA genes (rDNA). This is an example of gene redundancy Why might organisms have lots of RNA genes? RNA codes for proteins – proteins are vital for all life functions CENTRAL DOGMA DNA → RNA → PROTEIN

Inversions Inversion - chromosomal fragment reattaches to original chromosome, but in reverse orientation In an inversion, a segment of a chromosome is turned around 180° within the chromosome

Inversions An inversion requires two breaks in the chromosome and subsequent reinsertion of the inverted segment. An inversion may arise from chromosomal looping

Pericentric inversion does change the relative lengths of the arms Paracentric inversion - does not change the relative lengths of the two arms of a chromosome Pericentric inversion does change the relative lengths of the arms Figure 8-19 One possible origin of a pericentric inversion.

Synapsis of inverted chromosomes requires an inversion loop

Translocations Translocation - chromosomal fragment joins a nonhomologous chromosome Translocations are either reciprocal or non-reciprocal Reciprocal: the exchange of segments between two nonhomologous chromosomes and has an unusual synapsis configuration during meiosis Non-reciprocal: the movement of a segment to another nonhomologous chromosome

Figure 8-14e Copyright © 2006 Pearson Prentice Hall, Inc. Place 08_14e.jpg here Figure 8-14e Overview of the five different types of rearrangement of chromosome segments. Figure 8-14e Copyright © 2006 Pearson Prentice Hall, Inc.

Robertsonian Translocation Robertsonian translocation (centric fusion) -involves breaks at the extreme ends of the short arms of two nonhomologous acrocentric chromosomes Familial Down syndrome is an example of this

Figure 8-24 Copyright © 2006 Pearson Prentice Hall, Inc. Figure 8-24 The possible origin of a Robertsonian translocation. Two independent breaks occur within the centromeric region on two nonhomologous chromosomes. Centric fusion of the long arms of the two acrocentric chromosomes creates the unique chromosome. Two acentric fragments remain. Figure 8-24 Copyright © 2006 Pearson Prentice Hall, Inc.

Figure 8-251 Copyright © 2006 Pearson Prentice Hall, Inc. Figure 8-251 Chromosomal involvement in familial Down syndrome. The photograph illustrates the relevant chromosomes from a trisomy 21 offspring produced by a translocation carrier parent. Figure 8-251 Copyright © 2006 Pearson Prentice Hall, Inc.

Translocation disorders Implicated in certain cancers, including chronic myelogenous leukemia (CML) Fragment of chrom 22 swaps with a small fragment from tip of chrom 9 Familial Down Syndrome Normal # of chrom, but have all/part of 3 chrom 21 attached by translocation

Fragile Sites Fragile sites are more susceptible to chromosome breakage when cells are cultured in the absence of certain chemicals such as folic acid.

Fragile X Syndrome Fragile X syndrome - various degrees of mental retardation Abnormal X chromosome - tip hangs on by a thin thread of DNA 1/4000 males & 1/8000 females Complex inheritance, but syndrome more common when abnormal chrom inherited from mom Consistent with higher freq in males Imprinting by mom somehow causes it

Figure 8-26 Copyright © 2006 Pearson Prentice Hall, Inc. Figure 8-26 A normal human X chromosome (left) contrasted with a fragile X chromosome (right). The [[p]]gap[[p]] region (near the bottom of the chromosome) is associated with the fragile X syndrome. Figure 8-26 Copyright © 2006 Pearson Prentice Hall, Inc.