13 VARIATION IN CHROMOSOME NUMBER & STRUCTURE3.1 Chromosome Number in Different SpeciesIn "higher” organisms (diploids), members of same species typically have identical numbers ofchromosomes in each somatic cell. Diploid chromosome number (2n). Nearly allchromosomes will exist in pairs (identical wrt length and centromere placement) except the sexchromosomes. Members of pair are homologous chromosomes. Haploid number (n) isthe number of chromosome pairs. 2n nHuman 46 23Horse 64 32Cat 38 19Geometrid moth224112Tomato 24 12Pink bread mold 14 7See other examples in text3.2 Autosomal monosomy and trisomyOccasionally, one finds an organism that has an extra copy of a particular chromosome. Thisis known as trisomy--because there are now 3 copies of an autosome. Some trisomies areviable in animals, but the condition usually has severe effects. These effects are presumablyrelated to the fact that there are 3 copies of every gene on the trisomic chromosome, but only2 copies of all the genes on the other chromosomes. We will see later, that organisms withthree 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 22,2plus 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 750live births produces a child with this condition. It results from the non-disjunction ofchromosome 21 during meiotic anaphase I or anaphase II, when the paired homologs (orpaired chromatids) normally migrate to opposite poles of the cell.Nondisjuction: The members of a chromosome pair (homologs) line up at the metaphaseplate during meiotic metaphase I, then separate to opposite poles of the cell during anaphaseI--review this material in Cambell or any introductory Genetics text if you are not thoroughlyfamiliar with it!). If the pair fails to separate, and both migrate to the same pole, half of theresulting gametes will have two copies of chromosome 21, rather than one. When this gameteunites with a normal gamete (bearing one copy of chromosome 21) during fertilization, theresulting gamete has 3 copies of chromosome 21, rather than the normal 2. Non-disjunction ofchromosome 21 seems to occur more often in the production of eggs than sperm, and thefrequency increases with the age of the parent. Older individuals are often encouraged to testfor trisomy 21 by amniocentesis at 15 to 16 weeks after conception. Non-disjunction canhappen to other chromosomes in addition to chromosome 21. But human embryos that aretrisomic 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 atanaphase 1 will have 0 copies of the chromosome. When a gamete with 0 copies of achromosome unites with a normal gamete, the result is a zygote that has only one copy of thatchromosome. This is monosomy. Monosomy is not well tolerated in animals--usuallylethal. Some plants can survive (observed in maize, tomato, Oenothera, and Datura) but theyhave low viability and are usually sterile.Nondisjunction can also occur at anaphase II, when sister chromatids fail to separate andmigrate to opposite poles. Nondisjuntion at anaphase one results in half the gametes beingnormal, and half being abnormal (see diagram in text).If one surveys karyotypes of embryos that spontaneously abort, trisomies for all the autosomesare seen, and other forms of chromosomal abnormalities as well, but these conditions areapparently fatal early in development. Normal embryonic development requires a precisediploid complement of chromosomes.Chromosomal Abnormalities Occurring in Human FetusesType of Abnormality% spontaneously abortedfetuses with abnormality% fetuses with theabnormalitysurviving to termAll abnormalities505Autosomal trisomies 167.50 13, 18, & 214.515 All others13.80Trisomies of sex chromosomesXXX, XXY, XYY0.375Monosomy for X (XO)8.71Structural abnormalities20453Exception to general lethality of monosomies and trisomies occurs if they involve mammaliansex chromosomes. These monosomies and trisomies are often viable because of X-inactivation and because the Y contains few genes. We will discuss X inactivation later in thiscourse.An extra X chromosome also has fewer deleterious effects than an extra autosome. This isbecause, in mammals, all X chromosomes except one are inactivated very early in embryonicdevelopment. If this were not the case, then females would have twice as many active X-linked genes as males, and would therefore have twice as much of all the protein productsproduced by these genes. The inactivation of one of the two X chromosomes in femaleequalizes the gene dosage of X-linked genes--dosage compensation. This topic will becovered in more detail in a later lecture.3.3 Chromosomal Rearrangements:We have so far considered only variation in chromosome number. Variations in chromosomestructure also exist, and also cause characteristic genetic effects. We will consider deletionsand duplications of parts of whole chromosomes, and inversions and translocations of sectionsof chromosomes.3.3.1 DeletionsSometimes a chromosome will arise in which a segment is missing. These chromosomes aresaid 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, becausethe other chromosome contains copies of the genes missing in the chromosome with thedeletion. But even small deletions are usually lethal if they are homozygous. A deletion on onehomologue can “unmask” recessive alleles on the other homologue--this effect is calledpseudo-dominace. a———----———•———— ——————•———— & ---- region lost at meiosisHeterozygote 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——————————•———