5

Human Karyotypes and Chromosome

Behavior

Human Chromosomes

• Humans contain 46 chromosomes, including 22 pairs of homologous chromosomes and two sex chromosomes

• Karyotype = stained and photographed preparation of metaphase chromosomes arranged in homologous pairs in descending size order

Human Chromosomes

• Chromosome maps are prepared by dividing the chromosome 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

Centromeres

Centromeres may be located in different regions of a chromosome:

• Metacentric = located in middle of chromosome

• Submetacentric = located closer to one end of chromosome

• Acrocentric = located near one end of chromosome

Human X Chromosome• Females=2 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• Dosage Compensation=

dosage equalization for active genes

Human Y Chromosome

• Y chromosome is largely heterochromatic (condensed inactive chromatin)

• Important regions of Y chromosome:

-pseudoautosomal region=region of shared X-Y homology

-SRY=master sex controller gene which encodes testis determining factor (TDF) for male development

Abnormal Chromosome Number

• Euploid=balanced chromosome abnormality=equal number of copies

• aneuploid=unbalanced set of chromosomes=unequal copy number

• monosomic=loss of a single chromosome copy

Abnormal Chromosome Number

• Trisomy of chromosome 21 = most common autosomal (non-sex chromosome) aneuploidy

• Down Syndrome = genetic disorder due to trisomy 21 = aneuploidy

• Amniocentesis=fetal cells are analyzed for abnormalties of chromosome number and structure

Extra or Missing Chromosomes• Polysomy = extra copies of single chromosomes in a

cell• Trisomy = extra copy

of chromosome• Trivalent = abnormal

pairing of trisomic chromosomes in cell division

• Univalent = extra chromosome in trisomy is unpaired in cell division

Sex Chromosome Aneuploidies

• trisomy-X=47, XXX (female)• double-Y=47, XYY (male)• Klinefelter Syndrome=47, XXY (male,

sterile)• Turner Syndrome=45, X (female, sterile)• Fragile-X syndrome= X chromosome

instability resulting from high copy number of trinucleotide repeat

Chromosome Deletions

• Deletions = missing chromosome segment• Polytene chromosomes of Drosophila can be

used to map physically the locations of deletions

• Testcross mapping shows which wild-type alleles are lost by deletion

• Large deletions are often lethal

Gene Duplications

• Duplication = 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 recombi-nation

Red-Green Color Vision Genes

• Green-pigment genes may be present in multiple copies on the X-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

• Results in chimeric (composite) gene

Chromosome Inversions

• Inversions = genetic rearrangements in which the order of genes is reversed in a chromosome segment

• Inversions do not alter the genetic content but change the linear sequence of genetic information

• At synapsis = homologous pairing, inversion loops form

Chromosome Inversions

• Paracentric inversion = does not include centromere; Pericentric inversion = includes centromere

• Crossing-over within a paracentric inversion loop during recombination produces one acentric (no centromere) and one dicentric (two centromeres) chromosome

Chromosome Inversions

• Crossing-over within a pericentric inversion loop during homologous recombination results in duplications and deletions of genetic information

• Deletions and duplications occur because inversion loop causes misalignment of chromosomes during homologous pairing = synapsis

Reciprocal Translocations

• Reciprocal translocations = exchange of genetic segments between non-homologous (unrelated) chromosomes

• There is no loss of genetic information but the functions of specific genes may be altered

• Reciprocal translocation may affect one or both pairs of chromosomes

Reciprocal Translocation

• Heterozygous translocation = only one pair of non-homologous chromosomes is affected

• Homozygous translocation = both pairs of non-homologous chromosomes are affected

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 varying genetic outcomes in gametes

Reciprocal Translocation

3 outcomes of meiotic segregation:• Adjacent-1 segregation: homologous

centromeres separate at anaphase I; gametes contain duplications and deletions

• Adjacent-2 segregation: homologous centromeres stay together at anaphase I; gametes have a segment duplication and deletion

Reciprocal Translocation

• Alternate Segregation: half the gametes receive both parts of the reciprocal translocation and the other half receive both normal chromosomes; all gametes are euploid = normal genetic content, but half are translocation carriers

Robertsonian Translocation

• 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

Robertsonian Translocation

Meiotic segregation (14:21):• Adjacent-1 segregation: 1/2 gametes have

extra copy of most of chromosome 21 (fertilization will produce Down Syndrome = trisomy 21); 1/2 gametes have no copy of 21

• Adjacent-2 segregation: 1/2 gametes contain duplications; 1/2 lack chromosome 14

Robertsonian Translocation

• Alternate Segregation: all gametes are euploid; 1/2 are carriers of the Robertsonian translocation

• Translocations may produce position effects = changes in gene function due to repositioning of gene

• Gene expression = elevated or decreased in translocated gene

Polyploidy• Polyploidy = genome composed

of multiple complete sets of chromosomes; occurs in plants

• Haploid = set of unpaired chromosomes found in gametes

• Diploid = set of paired homologous chromosomes found in most cells; total number is fixed for a species

Chromosome Number

• monoploid = basic set of chromosomes; number fixed for species

• diploid = 2 copies of monoploid set• triploid = 3 copies of monoploid set• tetraploid = 4 copies of monoploid set• hexaploid = 6 copies of monoploid set

Endoreduplication

• Endoreduplication=doubling of the chromosome complement

• Tetraploidy=chromosomes fail to segregate during meiosis or mitosis

• autopolyploidy=chromosomes derived from single diploid

• Chromosome painting = chromosomes hybridized with fluorescent dye to show origins