Concepts and Connections Benjamin A. Pierce GENETICS ESSENTIALS Concepts and Connections SECOND EDITION CHAPTER 6 Chromosome Variation © 2013 W. H. Freeman and Company

The case of down syndrome Chromosome 21 and the Down Syndrome Critical Region: 5 million base pair region 33 genes Still not clear Indicates complex gene Interactions at chromosome 21 Down syndrome is caused by the presence of three copies of one or more genes located on chromosome 21.

Chapter 6 Outline 6.1 Chromosome Mutations Include Rearrangements, Aneuploids, and Polyploids, 148 6.2 Chromosome Rearrangements Alter Chromosome Structure, 150 6.3 Aneuploidy Is an Increase or Decrease in the Number of Individual Chromosomes, 159 6.4 Polyploidy Is the Presence of More Than Two Sets of Chromosomes, 163 6.5 Chromosome Variation Plays an Important Role in Evolution, 168

6.1 Chromosome Mutations Include Rearrangements, Aneuploids, and Polyploids Chromosome Morphology: (position of the centromere on the chromosome) Metacentric Submetacentric Acrocentric Telocentric Karyotype Complete set of chromosomes

6.1 Chromosome Mutations Include Rearrangements, Aneuploids, and Polyploids Types of Chromosome Mutations: Rearrangements: Aneuploidy Polyploidy

6.2 Chromosome Rearrangements Alter Chromosome Structure Duplication: Tandem ABoCDEFEFG Displaced ABoCDEFGEF Or to other chromosome Reverse ABoCDEFFEG What are the consequences?

The bar mutation and duplication in Drosophila Bar mutation reduces the number of facets in the eye Heterozygous females and hemizygous males carrying the mutation have smaller eyes.

How does the duplication affect phenotype? Not well understood but gene dosage is main suspect Interactions of many gene products influence development Or novel functions Human globin genes Segmental duplications on one chromosome (intrachromosmal) or on different chromosomes (interchromosomal)

6.2 Chromosome Rearrangements Alter Chromosome Structure Deletions ABoCDEFG becomes ABoCD/G Observable on metaphase chromosomes similar to duplications have looping. Consequences: Homozygous lethal Heterozygous: Imbalance Pseudodominance Haploinsufficient gene

6.2 Chromosome Rearrangements Alter Chromosome Structure Inversions (depending on the involvement of centromere): ABoCDEFG becomes ABoCFEDG (paracentric) ABoCDEFG becomes ADCoBEFG (pericentric) Consequences (even no genetic material is delted or gained): Gene break Position effect

Translocation Nonreciprocal translocation Reciprocal translocation ABoCDEFG and MNoOPQRS leads to ABoCDG and MNoOPEFQRS Reciprocal translocation ABoCDEFG and MNoOPQRS leads to ABoCDQRG and MNoOPEFS Consequences: Fused genes leading to fusion proteins Position effect Break within a gene Robertsonian translocation

6.3 Aneuploidy Is an Increase or Decrease in the Number of Individual Chromosomes Causes of Aneuploidy: Deletion of centromere during mitosis and meiosis Robertsonian translocation Nondisjunction during meiosis and mitosis

Types of Aneuploidy Nullisomy: loss of both members of a homologous pair of chromosomes. 2n − 2 Monosomy: loss of a single chromosome. 2n − 1 Trisomy: gain of a single chromosome. 2n + 1 Tetrasomy: gain of two homologous chromosomes. 2n + 2 More example 2n+1+1 (double trisomy) 2n-1-1 (double monosomy) 2n+2+2 (double tetrasomy)

Effects of Aneuploidy: 6.3 Aneuploidy Is an Increase or Decrease in the Number of Individual Chromosomes Effects of Aneuploidy: Mostly drastic effects Gene dosage Aneuploidy in humans: Sex-chromosome: Turner syndrome. XO Klinefelter sydrome. XXY

Effects of Aneuploidy: 9.3 Aneuploidy Is an Increase or Decrease in the Number of Individual Chromosomes Effects of Aneuploidy: In humans: Autosomal aneuploids: Trisomy 21 – Down sydrome Primary Down syndrome, 75% random nondisjunction in egg formation. Familial Down syndrome, Robertsonian translocation between chromosomes 14 and 21.

Carriers of translocations: increased risk for child with down syndrome Figure 6.21 Translocation carriers are at increased risk for producing children with Down syndrome.

Effects of Aneuploidy: 6.3 Aneuploidy Is an Increase or Decrease in the Number of Individual Chromosomes Effects of Aneuploidy: In humans: Autosomal aneuploids: Trisomy 18 – Edward syndrome, 1/8000 live births Trisomy 13 – Patau syndrome, 1/15,000 live births Trisomy 8 1/25,000 ~ 1/50,000 live births Why is there a drastic decrease in frequency of these trisomic syndromes from Chromosome 18 to Chromosome 8?

Effects of Aneuploidy: 6.3 Aneuploidy Is an Increase or Decrease in the Number of Individual Chromosomes Effects of Aneuploidy: In humans: Autosomal aneuploids: Aneuploidy and maternal age. Possible interpretation?

6.4 Polyploidy is the Presence of More Than Two Sets of Chromosomes Failure of whole sets of chromosomes to separate Tripolids (3n); tertaploids (4n), pentaploidsn (5n) Common in plants; less so in animals Autopolyploidy: From a single species

Unbalanced chromosomes after meiosis of a triploid cell

6.4 Polyploidy is the Presence of More Than Two Sets of Chromosomes Allopolyploidy From two species Creation of amphidiploid

6.4 Polyploidy is the Presence of More Than Two Sets of Chromosomes The significance of polyploidy: Nuclear volume increases-cell volume increases Selection of plants with bigger leaves, flowers, fruits, seeds.

6.5 Chromosome Variation Plays an Important Role in Evolution New and extra copies of genes give rise to new functions. New and extra sets of genes may give rise to new species.