3 3 1 VARIATION IN CHROMOSOME NUMBER STRUCTURE Chromosome Number in Different Species In higher organisms diploids members of same species typically have identical numbers of chromosomes in each somatic cell Diploid chromosome number 2n Nearly all chromosomes will exist in pairs identical wrt length and centromere placement except the sex chromosomes Members of pair are homologous chromosomes Haploid number n is the number of chromosome pairs Human Horse Cat Geometrid moth Tomato Pink bread mold See other examples in text 3 2 2n 46 64 38 224 24 14 n 23 32 19 112 12 7 Autosomal monosomy and trisomy Occasionally one finds an organism that has an extra copy of a particular chromosome This is known as trisomy because there are now 3 copies of an autosome Some trisomies are viable in animals but the condition usually has severe effects These effects are presumably related to the fact that there are 3 copies of every gene on the trisomic chromosome but only 2 copies of all the genes on the other chromosomes We will see later that organisms with three or more copies of all the chromosomes are often perfectly viable Trisomy of human chromosome 21 is the cause of the disorder known as Down syndrome Remember humans have 23 pairs of chromosomes the pairs are numbered 1 through 22 1 plus the X and Y It is characterized by multiple physical defects including epicanthal fold furrowed tongue characteristic palm and finger print patterns and lowered IQ About 1 in 750 live births produces a child with this condition It results from the non disjunction of chromosome 21 during meiotic anaphase I or anaphase II when the paired homologs or paired chromatids normally migrate to opposite poles of the cell Nondisjuction The members of a chromosome pair homologs line up at the metaphase plate during meiotic metaphase I then separate to opposite poles of the cell during anaphase I review this material in Cambell or any introductory Genetics text if you are not thoroughly familiar with it If the pair fails to separate and both migrate to the same pole half of the resulting gametes will have two copies of chromosome 21 rather than one When this gamete unites with a normal gamete bearing one copy of chromosome 21 during fertilization the resulting gamete has 3 copies of chromosome 21 rather than the normal 2 Non disjunction of chromosome 21 seems to occur more often in the production of eggs than sperm and the frequency increases with the age of the parent Older individuals are often encouraged to test for trisomy 21 by amniocentesis at 15 to 16 weeks after conception Non disjunction can happen to other chromosomes in addition to chromosome 21 But human embryos that are trisomic for any other chromosome do not survive to birth It should be obvious that the other half of the gametes resulting from a non disjunction event at anaphase 1 will have 0 copies of the chromosome When a gamete with 0 copies of a chromosome unites with a normal gamete the result is a zygote that has only one copy of that chromosome This is monosomy Monosomy is not well tolerated in animals usually lethal Some plants can survive observed in maize tomato Oenothera and Datura but they have low viability and are usually sterile Nondisjunction can also occur at anaphase II when sister chromatids fail to separate and migrate to opposite poles Nondisjuntion at anaphase one results in half the gametes being normal and half being abnormal see diagram in text If one surveys karyotypes of embryos that spontaneously abort trisomies for all the autosomes are seen and other forms of chromosomal abnormalities as well but these conditions are apparently fatal early in development Normal embryonic development requires a precise diploid complement of chromosomes Chromosomal Abnormalities Occurring in Human Fetuses fetuses with the spontaneously aborted abnormality Type of Abnormality fetuses with abnormality surviving to term All abnormalities 50 5 Autosomal trisomies 16 7 5 0 13 18 21 4 5 15 All others 13 8 0 Trisomies of sex chromosomes XXX XXY XYY 0 3 75 Monosomy for X XO 8 7 1 Structural abnormalities 20 45 2 Exception to general lethality of monosomies and trisomies occurs if they involve mammalian sex chromosomes These monosomies and trisomies are often viable because of Xinactivation and because the Y contains few genes We will discuss X inactivation later in this course An extra X chromosome also has fewer deleterious effects than an extra autosome This is because in mammals all X chromosomes except one are inactivated very early in embryonic development If this were not the case then females would have twice as many active Xlinked genes as males and would therefore have twice as much of all the protein products produced by these genes The inactivation of one of the two X chromosomes in female equalizes the gene dosage of X linked genes dosage compensation This topic will be covered in more detail in a later lecture 3 3 Chromosomal Rearrangements We have so far considered only variation in chromosome number Variations in chromosome structure also exist and also cause characteristic genetic effects We will consider deletions and duplications of parts of whole chromosomes and inversions and translocations of sections of chromosomes 3 3 1 Deletions Sometimes a chromosome will arise in which a segment is missing These chromosomes are said to have deletions Deletions are generally harmful and typically the larger the deletion the more harmful it is Small deletions are often viable if the deletion is heterozygous because the other chromosome contains copies of the genes missing in the chromosome with the deletion But even small deletions are usually lethal if they are homozygous A deletion on one homologue can unmask recessive alleles on the other homologue this effect is called pseudo dominace a region lost at meiosis Heterozygote for deletion during Meiotic pairing of homologs a any recessive genes will be expressed pseudodominance Unmatched part of top chromosome forms a loop Deletion loop see text Homozygotes for deletions often lethal 3 3 2 Duplications A B C D E A B C B C D E 3 Duplication often results in reduction of viability but in general duplications are less severe in their effects than are deletions Heterozygote for duplication during meiotic pairing of homologs A B C B C D E A B C D E Unmatched part of top chromosome forms a loop Duplication loop see notes Heterozygotes and homozygotes for small duplications can be viable although