Genetics - chromosome variation and sex determination

What is an individual’s karyotype?

An individual’s complete set of chromosomes or a lab-produced image of a person’s isolated chromosomes

What can a karyotype be used for?

Look for abnormalities in chromosome number or structure

Which human cells are haploid versus diploid?

• Haploid - sperm and egg cells

• Diploid - somatic (body) cells

What are polyploids?

Individuals with more than two chromosome sets

What are euploids?

Individuals with more than two copies of a single chromosome

What are the possible forms of polyploidy?

Triploid, tetraploid, pentaploid, and more

Does polyploidy always cause abnormal development?

• No

• Male bees, wasps and ants are monoploid as they develop from unfertilised eggs

What are aneuploids?

Individuals whose chromosome number differs by one or a small number of chromosomes

What are the effects of monosomies in a genome?

• Humans die in utero if in autosomes

• Monosomy for X causes Turner syndrome (genotype XO)

• 75-80% of cases it is caused by a missing X chromosome in the father’s sperm

What are the effects of trisomies in a genome?

• Lethal

• Number of viable trisomies

• Trisomy 21 causes Down’s syndrome

• 90% of cases it is caused by non-disjunction in the mother’s egg

What are the effect of an XXY genome?

• Causes Klinefelter syndrome

• Extra chromosome can come from the mother or the father

Why do gene balances in a genome cause phenotypic effects?

• Genes have evolved to function in a diploid genetic background so disrupting the background disrupts their function

• Explains why aneuploids are more abnormal than polyploids

• Haplo-abnormal genes - reduced copies of some genes compared to background

• Triplo-abnormal genes - increased copies of some genes compared to background

Why do expressions of deleterious alleles on monosomic autosomes have a phenotypic effect?

• Monosomics are typically more severe than trisomics

• Single copy of genes reveals deleterious alleles

How do duplications within a chromosome affect their structure and function?

• Duplications play an important role in evolution of the genome

• Can allow a gene to function if one copy is mutated and doesn’t work anymore

• Duplicated genes can evolve new functions if non-important within the organism

How do deletions within a chromosome affect their structure and function?

• Loss of part of one chromosome arm

• Can be small and only covering a part of one gene

• Can be large with chromosomes missing pieces large enough to be visualised in a karyotype

• Can use fluorescent in situ hybridisation (FISH) to visualise small sections of deleted DNA

• Use a fluorescent tag on a probe specific to a certain promoter sequence

How do copy number variations (CNVs) affect the chromosome’s structure and function?

• Chromosomes can have missing or extra pieces on one chromosome

• Copy/delete large sections of chromosomes

• See a peak/trough in the number of reads with CNVs due to duplication/deletion

How do inversions affect the chromosome’s structure and function?

• Can cause issues in meiosis and mitosis with chromosome alignments

• Can lead to non-disjunction

How do translocations affect the chromosome’s structure and function?

• Reciprocal and Robertsonian translocation

• No loss or gain of genetic information

• Linked to CML and the Philadelphia chromosome - caused by translocation between chromosomes 9 and 22

• Creates a fusion gene called BCR-ABL 1 that causes uncontrolled cell division

• Have been able to design drugs to work against the tyrosine protein

What type of sex determination system do mammals have?

XY determination system

• Females are XX

• Males are XY

What is present on the Y chromosome?

• Very few genes with mostly repeated sequences

• SRY - maleness-determining gene

• Father-son inheritance

Why is aneuploidy tolerated in sex chromosomes?

• One X chromosome is epigenetically inactivated early in development

• Inactivated X can be seen as highly condensed

• Inactivation is random in different cells

• Female body is a mosaic for genes on the X chromosome

What is an alternative sex determination system?

• ZW system

• Males are ZZ - homogametic sex

• Females are ZW

How can X-linked traits be identified for XY systems?

• More males than females express the trait

• Characteristic often skips a generation

• If the female expresses the trait all her male offspring with express the trait

What is the genetic basis for Patau syndrome?

• Trisomy for chromosome 13

• Causes a poor prognosis, most infants die within their first year of life

What is the genetic basis for Edwards syndrome?

• Trisomy for chromosome 18

• Causes a poor prognosis, most infants die within their first year of life

What is the genetic basis for Williams syndrome?

• Deletion on chromosome 7 which removes one elastin gene