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Genetics: gene

Bio 207 Introductory Genetics

Chapters 1 & 4 Textbook Required: iGenetics package. ISBN 9780133018905

Lecture 2 outline

How do genes control biochemical pathways? What is the relationship between genes and nonenzymatic proteins?

Phenylketonuria

OMIM 261600 Animal model: mouse

Flling (1934) described Phenylketonuria (PKU) which is a disorder of metabolism caused by a defect in phenylalanine hydroxylase (PAH). The role of the normal allele is to produce phenylalanine hydroxylase, so the role of the normal gene is revealed by what happens when the normal gene product is absent.

How does a mutant allele affect a gene product?

Beadle and Tatum used Neurospora crassa

Haploid fungus

A person with PKU marries a person with AKU. One of their children marries a person with AKU what genotypes and phenotypes of children can they have and in what proportions?

PKU = pp HH, AKU = PP hh Parents: Children: Grandchildren:

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How to grow a mould

Nutritional mutants

Provide all the required nutrients: complete medium Provide only the simplest most basic nutrients needed for growth: minimal medium

Wildtype Neurospora grows on minimal medium Nutritional mutants do not grow on minimal medium Nutritional mutants that grow on minimal medium + amino acid (e.g. Tryptophan) are auxotrophic for that amino acid.

Inducing variation in growth ability

Dissecting the pathway to methionine

Growth response on minimal medium + Strains WT May March February August Unknown Minimal + + Add A + + + Add H + + + + Add H + + + + + Add M + + + + + +

Mutagen (X-rays) were used to generate mutants Auxotrophic mutants (auxotrophs) would NOT grow on minimal medium because they would be unable to obtain the nutrient required from this medium Unlike the wildtype prototrophic strains (prototrophs) which can grow on minimal medium

Which of the strains are auxotrophs and which are prototrophs?

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How do genes control biochemical pathways?

Tay-Sachs

Beadle and Tatum proposed the one-gene-one-enzyme hypothesis One- gene-one polypeptide hypothesis:The majority of genes code for cellular proteins. Each gene encodes one polypeptide (the simplest building block of a protein). Updated because one enzyme (or protein) can have more than one polypeptide component each encoded by a different gene What evidence do we now have that this hypothesis is not completely supported?

OMIM 272800 A homozygous recessive mutation of a gene (Nacetylhexosaminidase )

The normal N-acetylhexosaminidase (Hex-A) enzyme in the lysosome is important for the normal breakdown of gangliosides

See Text p. 65

Sickle Cell Anemia

OMIM 603903 A mutation in the gene coding for Beta haemoglobin reduces the ability of the red blood cells to carry oxygen. Hb-A/Hb-S individuals (heterozygotes) have sickle cell trait

haemoglobin

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Cystic Fibrosis

OMIM 219700 and 602421 Homozygous recessive Most common severe form of CF patients have a mutation in a gene cystic fibrosis transmembrane conductance regulator (CFTR)

Delta F508 is a deletion in the DNA sequence at position 508 that results in the absence of phenylalanine What base pairs of DNA would be missing in F508?

Discuss Genetics
Lecture 2 outline

Gene:

Lecture topics

Chapter in text

How do genes control biochemical pathways? What is the relationship between genes and nonenzymatic proteins? Tutorial Quizzes: a randomly chosen question from the chapter questions

Molecular functional definition from text

A nuleotide sequence of DNA that specifies a polypeptide or RNA

Tutorial quizzes Jan 9-13 cover 4.1 to 4.9

Introduction to 207 Genetics Mutants and Genomes Mendel and others Chromosomal basis of inheritance Mendel and extranuclear inheritance Basic Chromosome Mapping Chromosomal mutations Genetics of development Genetics of cancer Population genetics Quantitative genetics Review

1&4 7 & (8) 11 12 13 14 16 19 20 21 22