Structural Abnormalities

Home , Cri du chat syndrome

Deletions

Translocations

Inversions

Duplications

Small or large

Mutation in one or many genes

Homozygosity or heterozygosity for each

Consequences for gene function

• 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

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

Prader-Willi Syndrome Angelman Syndrome Deletions in Chromosome 15

Deletions

Translocations

Inversions

Duplications

• Exchange of chromosomal segments between nonhomologous chromosomes

• Two major types –Reciprocal translocation

–Non-reciprocal translocation

Ig- myc

ABCDE ABMN Parent KLMN KLCDE Has complete information

Deletion and Normal gametes Duplication gametes

ABCDE ABMN ABCDE ABMN KLMN KLCDE ABMN KLMN

– 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

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

Deletions

Translocations

Inversions

Duplications

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

Antp required for identity of T2 (Wings and legs)

Expression of Antp in head results in legs forming in place of antennae

Deletions

Translocations

Inversions

Duplications

Chapter 6 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning Chapter 6 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning Chapter 6 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning Evolution of genes/gene families

Hemoglobin family

ß family α family

gene duplication (~ 450 million years ago) divergence myoglobin

gene duplication (~ 700 million years ago) divergence Primordial gene

• 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

Fig. 6.29

Fig. 6.30