2 Human ChromosomesHumans contain 46 chromosomes, including 22 pairs of homologous autosomes and two sex chromosomesKaryotype = stained and photographed preparation of metaphase chromosomes arranged according to their size and position of centromeres
5 Human ChromosomesEach chromosome in karyotype is divided into two regions (arms) separated by the centromerep = short arm (petit); q = long armp and q arms are divided into numbered bands and interband regions based on pattern of stainingWithin each arm the regions are numbered.
6 Centromeres In metacentric it is located in middle of chromosome • Chromosomes are classified according to the relative position of their centromeresIn metacentric it is located in middle of chromosomeIn submetacentric—closer to one end of chromosomeIn acrocentric—near one end of chromosomeChromosomes with no centromere, or with two centromeres, are genetically unstable
8 Human X Chromosome Females have two copies of X chromosome One copy of X is randomly inactivated in all somatic cellsFemales are genetic mosaics for genes on the X chromosome; only one X allele is active in each cellBarr body = inactive X chromosome in the nucleus of interphase cellsDosage Compensation = dosage equalization for active genes
10 Human Y Chromosome Y chromosome is largely heterochromatic Heterochromatin is condensed inactive chromatinImportant regions of Y chromosome:pseudoautosomal region = region of shared X-Y homologySRY=master sex controller gene which encodes testis determining factor (TDF) for male developmentThe pseudoautosomal region of the X and Y chromosomes has gotten progressively shorter in evolutionary time.
12 Human Y ChromosomeY 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 generationThe set of alleles at two or more loci present in a particular chromosome is called a haplotypeThe 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: trisomics)Aneuploid = unbalanced set of chromosomes = relative gene dosage is upset (example: trisomy of chromosome 21)Monosomic = loss of a single chromosome copyPolysomic = extra copies of single chromosomesChromosome abnormalities are frequent in spontaneous abortions.
14 Abnormal Chromosome Number Monosomy or trisomy of most human autosomes unviable. There are three exceptions: trisomies of 13, 18 and 21Down Syndrome is a genetic disorder due to trisomy 21, the most common autosomal aneuploidy in humansFrequency of Down Syndrome increases with mother’s ageAmniocentesis = fetal cells are analyzed for abnormalities of chromosome number and structureChorionic villus sampling (CVS) = cells from a zygote-derived embryonic membrane (the chorion) analyzed
15 Abnormal Chromosome Number Trisomic chromosomes undergo abnormal segregationTrivalent = abnormal pairing of trisomic chromosomes in cell divisionUnivalent = extra chromosome in trisomy is unpaired in cell division
17 Sex Chromosome Aneuploidies An extra X or Y chromosome usually has a relatively mild effectTrisomy-X = 47, XXX (female)Double-Y = 47, XYY (male)Klinefelter Syndrome = 47, XXY (male, sterile)Turner Syndrome = 45, X (female, sterile)
18 Chromosome Deletions Deletions = missing chromosome segment Polytene chromosomes of Drosophila can be used to map physically the locations of deletionsAny recessive allele that is uncovered by a deletion must be located inside the boundaries of the deletion = deletion mappingLarge deletions are often lethal
20 Gene DuplicationsDuplication = chromosome segment present in multiple copiesTandem duplications = repeated segments are adjacentTandem duplications often result from unequal crossing-over due to mispairing of homologous chromosomes during meiotic recombinationFig. 5.17
21 Red-Green Color Vision Genes Genes for red and green pigments are close on X-chromosomeGreen-pigment genes may be present in multiple copies on the chromosome due to mispairing and unequal crossing-overUnequal crossing-over between these genes during meiotic recombination can also result in gene deletion and color-blindnessCrossing-over between red- and green-pigment genes results in chimeric (composite) gene
22 Chromosome Inversions Inversions = genetic rearrangements in which the order of genes in a chromosome segment is reversedInversions do not alter the genetic content but change the linear sequence of genetic informationIn an inversion heterozygote, chromosomes twist into a loop in the region in which the gene order is invertedFig. 5.22
23 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
25 Chromosome Inversions Pericentric inversion = includes centromereCrossing-over within a pericentric inversion loop during homologous recombination results in duplications and deletions of genetic information
26 Reciprocal Translocations A chromosomal aberration resulting from the interchange of parts between nonhomologous chromosomes is called a translocationThere is no loss of genetic information but the functions of specific genes may be alteredTranslocations may produce position effects = changes in gene function due to repositioning of geneGene expression may be elevated or decreased in translocated gene
27 Reciprocal Translocation Heterozygous translocation = one pair interchanged, one pair normalHomozygous translocation = both pairs interchangedFig. 5.25
28 Reciprocal Translocations Synapsis involving heterozygous reciprocal translocation results in pairing of four pairs of sister chromatids = quadrivalentChromosome pairs may segregate in several ways during meiosis, with three genetic outcomes:Adjacent-1 segregation: homologous centromeres separate at anaphase I; gametes contain duplications and deletions
29 Reciprocal Translocation Adjacent-2 segregation: homologous centromeres stay together at anaphase I; gametes have a segment duplication and deletionAlternate 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
30 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 translocationThe 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
32 Robertsonian Translocation A special case of nonreciprocal translocation is aRobertsonian translocation = fusion of two acrocentric chromosomes in the centromere regionTranslocation results in apparent loss of one chromosome in karyotype analysisGenetic information is lost inthe tips of the translocatedacrocentric chromosomesFig. 5.27
33 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 syndromeThe heterozygous carrier is phenotypically normal, but a high risk of Down syndrome results from aberrant segregation in meiosisApproximately 3 percent of children with Down syndrome are found to have one parent with such a translocation
34 PolyploidyPolyploid species have multiple complete sets of chromosomesThe basic chromosome set, from which all the other genomes areformed, is called the monoploid setThe haploid chromosome set is theset of chromosomes present in a gamete, irrespective of the chromosome number in the species.Fig. 529
35 PolyploidyPolyploids can arise from genome duplications occurring before or after fertilizationTwo 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 chromosomesthe doubling of the chromosome number takes place in mitosis. Chromosome doubling through an abortive mitotic division is called endoreduplication
36 PolyploidyAutopolyploids have all chromosomes in the polyploid species derive from a single diploid ancestralAllopolyploids have complete sets of chromosomes from two or more different ancestral speciesChromosome painting = chromosomes hybridized with fluorescent dye to show their originsPlant cells with a single set of chromosomes can be cultured
38 PolyploidyThe grass family illustrates the importance of polyploidy and chromo-some rearrangements in genome evolutionThe cereal grasses (rice, wheat, maize, millet, sugar cane, sorghum, and other cereals) are our most important crop plantsTheir genomes vary enormously in size: from 400 Mb found in rice to 16,000 Mb found in wheat
39 PolyploidyIn 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 DNAEach of the conserved regions (synteny groups) can be identified in all the grasses and referred to a similar region in the rice genome.