BIOL 214 Chapter 12 Chromosomes and Human Genetics

Chromosomal Theory of Inheritance

Carl Correns – 1900

• First suggests central role for chromosomes

• Authored one of the scientific papers announcing rediscovery of Mendel’s work

Walter Sutton – 1902

• Chromosomal theory of inheritance

• Based on observations that similar chromosomes paired with one another during meiosis

Inheritance of eye color in fruit flies

T.H. Morgan – 1910

• Working with fruit fly, Drosophila melanogaster

• Discovered a mutant male fly with white eyes instead of red

• Crossed the mutant male to a normal red-eyed female

• All F1 progeny red eyed = dominant trait

Morgan crossed F 1 females × F 1 males

• F 2 generation contained red and white- eyed flies

• But all white-eyed flies were male

Conclusions

Testcross of a F1 female with a white- eyed male showed the viability of white-eyed females

• Morgan concluded that the eye color gene resides on the female X chromosome

• Traits determined by sex chromosome genes are sex-linked

Sex chromosomes

• Sex chromosomes are a pair of dissimilar chromosomes that still pair during meiosis and mitosis

• Sex determination in Drosophila is based on the number of X chromosomes

• 2 X chromosomes = female

• 1 X and 1 Y chromosome = male

Sex determination

• Sex determination varies across organisms:

• Is based on presence of a Y chromosome in humans

• 2 X chromosomes = female

• Having a Y chromosome (X Y) = male

• In birds, the male has two Z chromosomes and females are Z W

• Some insects are either X X (female) or XO (O indicating absence of a chromosome) in males

Sex chromosomes in humans

• Humans have 46 total chromosomes

• 22 pairs are autosomes, non-sex chromosomes

• 1 pair of sex chromosomes

• Y chromosome highly condensed

• Recessive alleles on male’s X have no active counterpart on Y

• “Default” for humans is female.

• Requires SRY gene on Y for

“maleness”

Sex Linkage

• In organisms with X Y sex-determination (like humans) few genes from Y chromosome are expressed

• Result is that recessive alleles on X chromosome have no active partner on Y, therefore, a single recessive sex-linked gene can produce recessive phenotype

• Certain genetic diseases affect males to a greater degree than

females as a result

• X-linked recessive alleles:

• Red-green color blindness

• Hemophilia

Dosage Compensation

• Ensures equal expression of genes from sex chromosomes even though number of chromosomes is different between sexes

• In mammalian female cells, 1 X chromosome is randomly inactivated and is highly condensed into a Barr body

• Females heterozygous for genes on the X chromosome are genetic mosaics

• Example: Calico cat

Chromosome theory exceptions

• Mitochondria and chloroplasts contain genes

• Traits controlled by these genes do not follow the chromosomal theory of inheritance

• Genes from mitochondria and chloroplasts are often passed to the offspring by only one parent, often the mother, called maternal inheritance

• In plants, chloroplasts are also often inherited from the mother, although this is species dependent

Genetic Mapping

• Early geneticists realized that they could obtain information about the distance between genes on a chromosome

• Distance estimates based on patterns of genetic recombination (crossing over) between genes

• If crossover occurs, parental alleles are recombined producing recombinant gametes

Recombination is the basis for genetic maps

Alfred Sturtevant

• Undergraduate in T.H. Morgan’s lab

• Put Morgan’s observation that recombinant progeny reflected relevant location of genes in quantitative terms

• As physical distance on a chromosome increases, so does the probability of recombination (crossover) occurring between the gene loci

Constructing Maps

Human Genetics: Mendelian Genes

Some human traits are controlled by a single gene

• Some of these exhibit dominant and recessive

inheritance, just like Mendel observed in pea plants

Pedigree analysis is used to track inheritance patterns in

families

• Dominant pedigree example – juvenile glaucoma

• Recessive pedigree example - albinism

Sex-linked human genetic disorders

• Some genetic disorders affect males more than females (that is sex-linked)

• Hemophilia is a disease that affects a single protein in a cascade involved in

formation of blood clots

• Form of hemophilia is caused by an X- linked recessive allele

• Heterozygous females are asymptomatic carriers

Cell Anemia is a recessive Disorder

A single amino acid change in a single protein can result in clinical syndrome

Example: Sickle cell anemia

• First human disease shown to be the result of a mutation in a protein

• Caused by a defect in the oxygen carrier molecule, hemoglobin

• Leads to impaired oxygen delivery to tissues

Sickle cell anemia

Homozygotes for sickle cell allele exhibit intermittent illness and reduced life span

• Heterozygotes appear normal

• Do have hemoglobin with reduced ability to carry oxygen

Sickle cell allele is particularly prevalent in people from areas with endemic Malaria.

• Proportion of heterozygotes higher than expected

• Confers resistance to blood-borne parasite that causes malaria, explains higher proportion of allele

Nondisjunction of autosomes

Human embryos trisomic for five of the smallest autosomes can survive birth

• Autosomes 13, 15, 18, 21 and 22

• 13, 15, 18 – severe defects, die within a few months

• 21 and 22 – can survive to adulthood

• Down syndrome – trisomy 21

• May be a full, third 21st chromosome

• May be a translocation of a part of chromosome 21

• Mother’s age influences risk

Nondisjunction of sex chromosomes

• Do not generally experience severe developmental abnormalities

• Individuals have somewhat abnormal features, but often reach maturity and in some cases may be fertile

• X X X – triple-X females

• X X Y – males (Klinefelter syndrome)

• X O – females (Turner syndrome)

• O Y – nonviable zygotes

• X Y Y – males (Jacob syndrome)