Structural Abnormalities Deletions Translocations Inversions Duplications Chapter 6

Chapter 6 Human Heredity by Michael Cummings © 2006 Brooks/Cole-Thomson Learning

Deletions Small or large Mutation in one or many genes Homozygosity or heterozygosity for each Consequences for gene function Chapter 6 Human Heredity by Michael Cummings © 2006 Brooks/Cole-Thomson Learning

Deletions • Loss of chromosomal material • Large-scale deletions are lethal • Example: Cri du chat – Deletion of short arm of chromosome 5 – Affects motor and mental function – Infant cry resembles a meowing cat – Specific chromosomal break points are associated with specific phenotypic changes Chapter 6 Human Heredity by Michael Cummings © 2006 Brooks/Cole-Thomson Learning

Cri du chat Syndrome Variation in phenotype associated with region deleted has been observed Researchers have identified regions with genes involved in larynx and nervous system development Fig. 6. 26 Chapter 6 Human Heredity by Michael Cummings © 2006 Brooks/Cole-Thomson Learning

Cri-du chat syndrome Deletion in Chrom. 5 Prader-Willi Syndrome Angelman Syndrome Deletions in Chromosome

Translocations • Exchange of chromosomal segments between nonhomologous chromosomes • Two major types – Reciprocal translocation – Non-reciprocal translocation Chapter 6 Human Heredity by Michael Cummings © 2006 Brooks/Cole-Thomson Learning

Types of Translocations Chapter 6 Human Heredity by Michael Cummings © 2006 Brooks/Cole-Thomson Learning

Burkitt’s lymphoma Ig- myc Chapter 6 Human Heredity by Michael Cummings © 2006 Brooks/Cole-Thomson

Reciprocal Translocation: yields normal and defective gamets v. ABCDE v. KLMN v. ABMN v. KLCDE Normal gametes v. ABCDE v. KLMN v. ABMN v. KLCDE Parent Has complete information Deletion and Duplication gametes v. ABCDE v. ABMN v. KLMN Chapter 6 Human Heredity by Michael Cummings © 2006 Brooks/Cole-Thomson Learning

Types of Translocations – Robertsonian Translocation • Centromeres from two nonhomologous chromosomes fuse and chromosomal material from the short arms is lost • 5% of Down syndrome cases involve a Robertsonian translocation between chromosomes 21 and 14 Chapter 6 Human Heredity by Michael Cummings © 2006 Brooks/Cole-Thomson Learning

Robertsonian Translocation A translocation between chromosome 14 and 21 may produce • Translocation carrier • Normal phenotype • Translocation Down syndrome • Lethal monosomy 21 • Lethal trisomy 14 • Lethal monosomy 14 Fig. 6. 27 Chapter 6 Human Heredity by Michael Cummings © 2006 Brooks/Cole-Thomson Learning

• Inversions reorganize DNA sequences New context Antennapedia • Antp protein is made in antennal primordial cells, where the WT Antp does not express • Legs grow out in Antp mutant in place of antenna Chapter 6 Human Heredity by Michael Cummings © 2006 Brooks/Cole-Thomson Learning

Wild-type head Antp expressed in head Antp required for identity of T 2 (Wings and legs) Expression of Antp in head results in legs forming in place of antennae Chapter 6 Human Heredity by Michael Cummings © 2006 Brooks/Cole-Thomson Learning

Evolution of genes/gene families Hemoglobin family ß family gene duplication divergence a family (~ 450 million years ago) myoglobin (~ 700 million years ago) Primordial gene Encodes O 2 carrier protein Chapter 6 Human Heredity by Michael Cummings © 2006 Brooks/Cole-Thomson Learning

Other Chromosomal Abnormalities • Uniparental disomy – Both copies of a chromosome are inherited from a single parent – Due to error in cell division – Examples • Females affected with rare X-linked disorders • Prader-Willi and Angelman syndromes • Fragile sites – Over 100 have been identified Chapter 6 Human Heredity by Michael Cummings © 2006 Brooks/Cole-Thomson Learning