Deviations from Mendel's Inheritance Model (College Board AP® Biology)

Gene Linkage

Patterns of Inheritance Are Not Always Predictable

• Some patterns of inheritance do not follow Mendel's laws

• Their observed phenotypic ratios among the offspring differ significantly from the predicted ratios

  • Gene linkage - means that some genes are not inherited independently of one another

  • Many traits are determined by multiple genes and physiological processes and therefore do not follow Mendelian patterns

Gene loci are said to be linked if they are on the same chromosome

• Loci (singular: locus) refers to the specific linear positions on the chromosome that genes occupy

• If genes are on the sex chromosome, they are said to be sex-linked

  • Sex-linked genes have characteristics that generally affect only one gender of a species

  • These genes are usually on the X chromosome because the Y chromosome contains very few genes

  • In humans, color blindness and hemophilia are notable examples of genetic conditions that only affect males

• Linked genes located on the chromosomes 1-22, or any chromosome that is not a sex chromosome (called autosomes) are said to be examples of autosomal linkage

• The likelihood of genes being inherited together, or the extent to which they are linked, is measured in units called centimorgans, in honor of Thomas Hunt Morgan, the geneticist that discovered the concept of linkage

Autosomal linkage

• Dihybrid crosses and their predictions rely on the assumption that the genes being investigated behave independently of one another during meiosis

• However, not all genes assort independently during meiosis

• Some genes which are located on the same chromosome display autosomal linkage and stay together in the original parental combination

• Linkage between genes affects how parental alleles are passed onto offspring through the gametes

• The distance between linked genes on a chromosome can be mapped using the probabilities that the linked genes will be inherited together

Identifying autosomal linkage from phenotypic ratios in crossing studies

• In the following theoretical example, a dihybrid cross is used to predict the inheritance of two different characteristics in a species of newt

  • The genes are for tail length and scale color

• The gene for tail length has two alleles:

  • Dominant allele T produces a normal length tail

  • Recessive allele t produces a shorter length tail

• The gene for scale color has two alleles:

  • Dominant allele G produces green scales

  • Recessive allele g produces white scales

Without linkage

• Normal Mendelian ratios would result if there is no linkage

• The outcomes for this dihybrid cross if the genes are unlinked are as follows

Dihybrid Cross without Linkage Punnett Square Table

• Predicted ratio of phenotypes in offspring =

  • 1 normal tail, green scales : 1 normal tail, white scales : 1 short tail, green scales : 1 short tail, white scales

• Predicted ratio of genotypes in offspring =

  • 1 TtGg : 1 Ttgg : 1 ttGg : 1 ttgg

With linkage

• However, if the same dihybrid cross is carried out but this time the genes are linked, we get a different phenotypic ratio

  • There would be a 1 : 1 phenotypic ratio (1 normal tail, green scales : 1 short tail, white scales)

  • This change in the phenotypic ratio occurs because the genes are located on the same chromosome

  • The unexpected phenotypic ratio, therefore, shows us that the genes are linked

• The explanation for this new phenotypic ratio is given in the worked example below:

Dihybrid Cross with Linkage Punnett Square Table

• Predicted ratio of genotypes in offspring =

  • 1 (TG)(tg) : 1 (tg)(tg)

• Predicted ratio of phenotypes in offspring =

  • 1 normal tail, green scales : 1 short tail, white scales

Sex Linkage

• Some genetic diseases in humans are sex-linked

• Inheritance of these diseases is different in males and females

  • Sex-linked genes are only present on one sex chromosome and not the other

  • This means the sex of an individual affects what alleles they pass on to their offspring through their gametes

• If the gene is on the X chromosome, males (XY) will only have one copy of the gene, whereas females (XX) will have two

• There are three phenotypes for females:

  • normal

  • carrier

  • has the disease,

• Males have only two phenotypes

  • normal

  • has the disease

• Hemophilia is a well known sex-linked disease

• There is a gene found on the X chromosome that codes for a protein called factor VIII

  • Factor VIII is needed to make blood clot

  • This can be dangerous as sufferers can often bleed out from an otherwise minor wound/injury

• There are two alleles for factor VIII

  • The dominant F allele which codes for normal factor VIII

  • The recessive f allele which results in a lack of factor VIII, meaning a person has hemophilia

• When a person possesses only the recessive allele f, they don’t produce factor VIII and their blood can't clot normally

• If males have an abnormal allele, f,  they will have the condition as they have only one copy of the gene

• Females can be heterozygous for the faulty gene and not suffer from the condition but act as a carrier

• This means that hemophilia is a potentially fatal genetic disease which affects males more than females

Monohybrid Punnett Square with Sex-linkage Table

Predicted ratio of phenotypes in offspring

1 female with normal blood clotting : 1 carrier female : 1 male with hemophilia : 1 male with normal blood clotting

Predicted ratio of genotypes in offspring: 1 X^FX^F : 1 X^FX^f : 1 X^FY : 1 X^fY

Non-Nuclear Inheritance

• Not all characteristics are determined by genes carried on chromosomes in the nucleus in eukaryotes

• Some genes are located within organelles elsewhere in the cell, away from the nucleus

• Mitochondria, chloroplasts (and other plastids) carry DNA

  • This non nuclear DNA is thought to date back to the origins of eukaryotic life, and gives further supporting evidence to the theory of endosymbiosis

• This DNA is not passed onto future generations in the same ways as nuclear DNA, so the traits it carries are inherited in non typical (non Mendelian) ways

  • The genes they carry are randomly assorted to daughter cells

• In animals, mitochondria are transmitted by the egg and not by sperm

  • Therefore, characteristics coded for in the mitochondrial DNA are inherited through the maternal line

• Similarly, iplants, mitochondria and chloroplasts are passed on in the ovule and not by the pollen

  • Therefore, characteristics coded for in the mitochondrial and chloroplast DNA are inherited through the maternal line