1. Chapter 5 Human Chromosomes and Chromosome Behavior

2. Human Chromosomes
Humans contain 46 chromosomes, including 22 pairs of homologous autosomes and two sex chromosomes
Karyotype = stained and photographed preparation of metaphase chromosomes arranged according to their size and position of centromeres

3. Figure 5.1A: Human chromosome painting
Figure 5.1B: Human chromosome painting
Parts A and B Courtesy of Johannes Wienberg, Ludwig-Maximillians-University, and Thomas Ried, National Institutes of Health

4. Centromeres
• Chromosomes are classified according to the relative position of their centromeres
In metacentric it is located in middle of chromosome
In submetacentric — closer to one end of chromosome
In acrocentric — near one end of chromosome
Chromosomes with no centromere, or with two centromeres, are genetically unstable

5. Human Chromosomes
Each chromosome in karyotype is divided into two regions (arms) separated by the centromere
p = short arm (petit); q = long arm
p and q arms are divided into numbered bands and interband regions based on pattern of staining
Within each arm the regions are numbered.

6. Figure 5.3: Designations of the bands and interbands in the human karyotype.

7. Human X Chromosome Females have two copies of X chromosome
One copy of X is randomly inactivated in all somatic cells.
Females are genetic mosaics for genes on the X chromosome; only one X allele is active in each cell.
Barr body = inactive X chromosome in the nucleus of interphase cells.
Dosage compensation equalizes the number of active copies of X-linked genes in females and males.

8. Figure 5.7: Schematic diagram of somatic cells of a normal female

9. The calico cat shows visible evidence of X-chromosome inactivation.
Figure 5.8: Female cat heterozygous for the orange and black coat color alleles

10. Human Y Chromosome
Y chromosome is largely heterochromatic.
Heterochromatin is condensed inactive chromatin.
Important regions of Y chromosome:
pseudoautosomal region: region of shared X-Y homology
SRY – master sex controller gene that encodes testis determining factor (TDF) for male development

11. The pseudoautosomal region of the X and Y chromosomes has gotten progressively shorter in evolutionary time.
Figure 5.9: Progressive shortening of the mammalian X-Y pseudoautosomal region through time
Data from B.T. Lahn and D.C. Page, Science 286 (1999):

12. Human Y Chromosome
Y chromosome does not undergo recombination along most of its length, genetic markers in the Y are completely linked and remain together as the chromosome is transmitted from generation to generation
The set of alleles at two or more loci present in a particular chromosome is called a haplotype
The history of human populations can be traced through studies of the Y chromosome

13. Abnormal Chromosome Number
Euploid = balanced chromosome abnormality = the same relative gene dosage as in diploids (example: tetraploids)
Aneuploid = unbalanced set of chromosomes = relative gene dosage is upset (example: trisomy of chromosome 21)
Monosomic = loss of a single chromosome copy
Polysomic = extra copies of single chromosomes
Chromosome abnormalities are frequent in spontaneous abortions.

14. Abnormal Chromosome Number
Monosomy or trisomy of most human autosomes is unviable. There are three exceptions: trisomies of 13, 18, and 21
Down Syndrome is a genetic disorder due to trisomy 21, the most common autosomal aneuploidy in humans
Frequency of Down Syndrome increases with mother’s age
Monosomy usually results in more harmful effects than trisomy

15. Abnormal Chromosome Number
Table 5.1 Chromosome Abnormalities per 100,000 Recognized Human Pregnancies

16. Abnormal Chromosome Number
Trisomic chromosomes undergo abnormal segregation
Trivalent = abnormal pairing of trisomic chromosomes in cell division
Univalent = extra chromosome in trisomy is unpaired in cell division

17. Figure 5.12: Meiotic synapsis in a trisomic

18. Sex Chromosome Aneuploidies
An extra X or Y chromosome usually has a relatively mild effect due to single-active-X principle and relatively few genes in Y chromosome
Trisomy-X = 47, XXX (female)
Double-Y = 47, XYY (male)
Klinefelter Syndrome = 47, XXY (male, sterile)
Turner Syndrome = 45, X (female, sterile)

19. Abnormal Chromosome Number
Aneuplody results from nondisjunction: a failure of chromosomes to separate and move to opposite poles of the division spindle
The rate of nondisjunction can be increased by chemicals in the environment.

20. Chromosome Deletions Deletions: missing chromosome segment
Polytene chromosomes of Drosophila can be used to map physically the locations of deletions
Any recessive allele that is uncovered by a deletion must be located inside the boundaries of the deletion: deletion mapping
Large deletions are often lethal

21. Figure 5.16: Part of the X chromosome in polytene salivary gland nuclei and the extent of six deletions (I–VI) in a set of chromosomes

22. Figure 5.17: Unequal crossing-over of tandem duplications
Gene Duplications
Duplication are genetics rearrangements in which chromosome segment present in multiple copies
Tandem duplications: repeated segments are adjacent
Tandem duplications often result from unequal crossing-over due to mispairing of homologous chromosomes during meiotic recombination
Figure 5.17: Unequal crossing-over of tandem duplications

23. Red-Green Color Vision Genes
Genes for red and green pigments are close on X-chromosome
Green-pigment genes may be present in multiple copies on the chromosome due to mispairing and unequal crossing-over
Unequal crossing-over between these genes during meiotic recombination can also result in gene deletion and color-blindness
Crossing-over between red- and green-pigment genes results in chimeric (composite) gene

24. Figure 5.19: Red-pigment and green-pigment genes

25. Chromosome Inversions
Inversions are genetic rearrangements in which the order of genes in a chromosome segment is reversed
Inversions do not alter the genetic content but change the linear sequence of genetic information
In an inversion heterozygote, chromosomes twist into a loop in the region in which the gene order is inverted
Figure 5.22: Loop in the region in which the gene order is inverted

26. Chromosome Inversions
Paracentric inversion does not include centromere
Crossing-over within a paracentric inversion loop during recombination produces one acentric (no centromere) and one dicentric (two centromeres) chromosome

27. Figure 5.23: Crossover within the inversion loop

28. Chromosome Inversions
Pericentric inversion includes centromere
Crossing-over within a pericentric inversion loop during homologous recombination results in duplications and deletions of genetic information
Figure 5.24: Synapsis between homologous chromosomes

29. Reciprocal Translocations
A chromosomal aberration resulting from the interchange of parts between nonhomologous chromosomes is called a translocation
There is no loss of genetic information, but the functions of specific genes may be altered
Translocations may produce position effects: changes in gene function due to repositioning of gene
Gene expression may be elevated or decreased in translocated gene

30. Reciprocal Translocation
In heterozygous translocation, one pair of chromosomes interchanged their segments and one pair is normal
In homozygous translocation, both pairs interchanged their segments
Figure 5.25: Two pairs of nonhomologous chromosomes in a diploid organism

31. Reciprocal Translocations
Synapsis involving heterozygous reciprocal translocation results in pairing of four pairs of sister chromatids – quadrivalent
Chromosome pairs may segregate in several ways during meiosis, with three genetic outcomes: adjacent-1 segregation, homologous centromeres separate at anaphase I, and gametes contain duplications and deletions

32. Reciprocal Translocation
Adjacent-2 segregation: homologous centromeres stay together at anaphase I; gametes have a segment duplication and deletion
Alternate segregation: half the gametes receive both parts of the reciprocal translocation and the other half receive both normal chromosomes; all gametes are euploid, i.e. have normal genetic content, but half are translocation carriers

33. Reciprocal Translocation
The duplication and deficiency of gametes produced by adjacent-1 and adjacent-2 segregation results in the semisterility of genotypes that are heterozygous for a reciprocal translocation
The frequencies of each outcome is influenced by the position of the translocation breakpoints, by the number and distribution of chiasmata, and by whether the quadrivalent tends to open out into a ring-shaped structure on the metaphase plate

34. Figure 5.26: A quadrivalent

35. Robertsonian Translocation
A special case of nonreciprocal translocation is a
Robertsonian translocation – fusion of two acrocentric chromosomes in the centromere region
Translocation results in apparent loss of one chromosome in karyotype analysis
Genetic information is lost in
the tips of the translocated
acrocentric chromosomes
Figure 5.27: Formation of a Robertsonian
translocation by fusion

36. Robertsonian Translocation
Robertsonian translocations are an important risk factor to be considered in Down syndrome. When chromosome 21 is one of the acrocentrics in a Robertsonian translocation, the rearrangement leads to a familial type of Down syndrome
The heterozygous carrier is phenotypically normal, but a high risk of Down syndrome results from aberrant segregation in meiosis
Approximately 3 percent of children with Down syndrome are found to have one parent with such a translocation

37. Polyploidy
Polyploid species have multiple complete sets of chromosomes
The basic chromosome set, from which all the other genomes are formed, is called the monoploid set
The haploid chromosome set is the set of chromosomes present in a gamete, irrespective of the chromosome number in the species.
Figure 5.29: Chromosome numbers in diploid and
polyploid species of Chrysanthemum

38. Polyploidy
Polyploids can arise from genome duplications occurring before or after fertilization
Two mechanisms of asexual polyploidization:
the increase in chromosome number takes place in meiosis through the formation of unreduced gametes that have double the normal complement of chromosomes
the doubling of the chromosome number takes place in mitosis. Chromosome doubling through an abortive mitotic division is called endoreduplication

39. Polyploidy
Autopolyploids have all chromosomes in the polyploid species derive from a single diploid ancestral
Allopolyploids have complete sets of chromosomes from two or more different ancestral species
Chromosome painting: chromosomes hybridized with fluorescent dye to show their origins
Plant cells with a single set of chromosomes can be cultured

40. Figure 5.31: Chromosome sets

41. Polyploidy
The grass family illustrates the importance of polyploidy and chromosome rearrangements in genome evolution
The cereal grasses (rice, wheat, maize, millet, sugar cane, sorghum, and other cereals) are our most important crop plants
Their genomes vary enormously in size: from 400 Mb found in rice to 16,000 Mb found in wheat

42. Polyploidy
In spite of the large variation in chromosome number and genome size, there are a number of genetic and physical linkages between single-copy genes that are remarkably conserved in all grasses amid a background of rapidly evolving repetitive DNA
Each of the conserved regions (synteny groups) can be identified in all the grasses and referred to a similar region in the rice genome.

43. Figure 5.35: Conserved linkages (synteny groups)
Data from G. Moore, Curr. Opin. Genet. Dev. 5 (1995):