Figure 2.16 Crossing over during meiosis

      So, the fourth principle considers genes transmitted on different chromosomes and that the transmission of one gene does not influence that of another gene. Independent assortment is explained through meiotic cell division. Chapter 5 looks at the inheritance of polygenic traits (multiple genes) in more detail.

      The eldest son of two curly black-haired parents also has curly black hair. The middle son has straight black hair and the youngest son has curly blond hair. Which of the following Mendelian principles does this illustrate? Dominance, segregation or independent assortment?

      EXCEPTIONS TO THE RULES

      Mendelian genetics explains the rules of recessive and dominant inheritance. In the last 100 years the science of genetics has developed, giving us more understanding of how traits are inherited on a biological level. Although Mendelian principles still hold true today, there are a few exceptions to the rules.

      1. Mitochondrial inheritance

      In addition to the 46 chromosomes within the cell’s nucleus, the mitochondria have their own genome. The mitochondrial DNA is not inherited in the same way as the nuclear DNA as it is only inherited from the mother and not from the father. Sperm never contribute mitochondria during the fertilisation of an ovum, so the mitochondrial genome within the ovum remains unchanged. This forms an exception to Mendel’s law of segregation in that both parents do not contribute equally mitochondrial DNA to their offspring.

      The mitochondrial DNA only forms a small part of the human genome. To date only 37 genes have been mapped to the mitochondrial DNA, most of which (24 genes) encode RNA molecules that are needed for protein synthesis within the cell’s cytoplasm. The remaining 13 genes encode for proteins that are needed for cellular respiration. The mitochondria, although it has its own genome, is still reliant on genes from the nuclear genome to function adequately.

      2. Penetrance

      Penetrance relates to the expression of phenotypic features by a single gene. All Mendelian inheritance has a 100 per cent penetrance, but not all inheritance occurs in a Mendelian fashion. The degree of penetrance is measured in percentages. For example, achondroplasia (dwarfism), which is inherited in an autosomal dominant fashion, shows 100 per cent penetrance. This means that all individuals who carry this dominant allele will display the effects of achondroplasia. Other dominant autosomal genes are not always expressed and are said to have reduced penetrance. Ectrodactyly, a condition where the central parts of the hands and feet are not adequately formed, is an example of reduced penetrance. Not all individuals who carry this dominant gene will have deformities in the hands and feet. Degrees of penetrance are measured according to how many people display the phenotype of the gene in question. The BRCA 1 gene defect, which can cause breast cancer, is measured at 75 per cent penetrance, in that 75 per cent of individuals who have this genotype will develop breast cancer and 25 per cent will not.

      3. Genomic imprinting

      The imprinting of genes is a mechanism where the expression of a gene is governed by whether it was inherited from the mother or the father. Imprinted genes do not fit into the usual rules of inheritance as the contribution from one parent has been silenced. Both dominant and recessive genes can be imprinted. These genes are ‘marked’ with the sex of the parent that contributed it. There is no change to the actual DNA structure within these genes but a molecule of methyl is attached to the gene.

      This process starts during gamete formation when certain genes are imprinted in either the developing sperm or the developing ovum. After fertilisation, the resulting offspring will have the same set of imprinted genes from both parents in all their somatic cells. However, the inherited imprinted genes will lose their methyl markers in the offspring’s germ cells (sperm or ova). The inherited markers are removed in the germ cells and are ‘reset’. This is done so that the new markers correspond to the offspring’s own sex. A particular gene can therefore be turned on or off as it is passed through successive generations, from male to female to male.

      The function of imprinted genes is not well understood. One possible reason for imprinting genes might be due to their role in embryonic development. Some genes lose their markers after birth, which suggests that imprinted genes may have an important role in regulating protein synthesis during pre-natal development.

      Imprinted genes are important for normal development and health. If an imprinted allele is not silenced the cell receives two active copies of the allele and this results in over-expression of that gene. Similarly, if both alleles are imprinted the result is under-expression of that gene. This is the reason that parthenogenesis (virgin birth) is not possible in humans. An offspring needs both male and female genes so that the right proportion of genes is activated.

      4. Sex-related effects

      Some phenotypic traits are not inherited in a Mendelian fashion as they may be influenced by the sex of the individual. Some traits will only be expressed in one sex and not another, like, for example, beard growth. This is an example of a sex-limited trait, as beard growth is limited to males (even though both sexes inherit the gene).

      Other traits can act as dominant in one sex and as recessive in the opposite sex. An example is male-patterned baldness in men. The allele for baldness acts as a dominant allele in males but as a recessive allele in females. This is known as a sex-influenced trait. (Females do not usually go bald, even with two recessive alleles for the baldness trait, due to the absence of necessary hormones.)

      5. Mutations

      A mutation is a permanent change in the sequence of chromosomal DNA. Mutated genes can be inherited in a Mendelian fashion. However, mutations can occur by chance and alter the genetic trait inherited by the offspring. For example, two parents of normal stature having a child with achondroplasia (dwarfism). As achondroplasia is due to a dominant gene, the affected offspring must have inherited or developed a change within the parental DNA because neither of the parents has achondroplasia.

      Dynamic mutations are progressive changes within the DNA that occur from one generation to the next. This usually involves expansion of the DNA molecule that encodes for a particular gene. The genetic disorder resulting from this mutation might not appear for a few generations until the DNA within the gene has reached a particular length. Fragile X syndrome and Huntington’s disease are just two examples of genetic conditions caused by dynamic mutations. Chapter 6 covers mutations in more detail.

      6.