Lethal Inheritance Patterns – Types, Structure, Functions

Lethal Inheritance Patterns

Lethal Inheritance Patterns

A large proportion of genes in an individual’s genome are essential for survival. Occasionally, a nonfunctional allele for an essential gene can arise by mutation and be transmitted in a population as long as individuals with this allele also have a wild-type, functional copy. The wild-type allele functions at a capacity sufficient to sustain life and is, therefore, considered to be dominant over the nonfunctional allele. However, consider two heterozygous parents that have a genotype of wild-type/nonfunctional mutant for a hypothetical essential gene. In one quarter of their offspring, we would expect to observe individuals that are homozygous recessive for the nonfunctional allele. Because the gene is essential, these individuals might fail to develop past fertilization, die in utero, or die later in life, depending on what life stage requires this gene. An inheritance pattern in which an allele is only lethal in the homozygous form and in which the heterozygote may be normal or have some altered non-lethal phenotype is referred to as recessive lethal.

For crosses between heterozygous individuals with a recessive lethal allele that causes death before birth when homozygous, only wild-type homozygotes and heterozygotes would be observed. The genotypic ratio would therefore be 2:1. In other instances, the recessive lethal allele might also exhibit a dominant (but not lethal) phenotype in the heterozygote. For instance, the recessive lethal Curly allele in Drosophila affects wing shape in the heterozygote form, but is lethal in the homozygote.

Dominant Lethal Alleles

Effects of Huntington’s disease on neurons: The neuron in the center of this micrograph (yellow) has nuclear inclusions characteristic of Huntington’s disease (orange area in the center of the neuron). Huntington’s disease occurs when an abnormal dominant allele for the Huntington gene is present.

Sex-Linked Traits

A gene present on one of the sex chromosomes (X or Y in mammals) is a sex-linked trait because its expression depends on the sex of the individual.

Sex Determination

In humans, as well as in many other animals and some plants, the sex of the individual is determined by sex chromosomes. However, there are other sex determination systems in nature. For example, temperature-dependent sex determination is relatively common,
and there are many other types of environmental sex determination. Some species, such as some snails, practice sex change adults start out male, then become female. In tropical clown fish, the dominant individual in a group becomes female while the others are male.

The sex chromosomes are one pair of non-homologous chromosomes. Until now, we have only considered inheritance patterns among non-sex chromosomes, or autosomes. In addition to 22 homologous pairs of autosomes, human females have a homologous pair of X chromosomes, whereas human males have an XY chromosome pair. Although the Y chromosome contains a small region of similarity to the X chromosome so that they can pair during meiosis, the Y chromosome is much shorter and contains many fewer genes. When a gene being examined is present on the X chromosome, but not on the Y chromosome, it is said to be X-linked.

X-Linked Traits

Eye color in Drosophila is an example of a X-linked trait: In Drosophila, the gene for eye color is located on the X chromosome. Clockwise from top left are brown, cinnabar, sepia, vermilion, white, and red. Red eye color is wild-type and is dominant to white eye color.

X-Linked Crosses

In an X-linked cross, the genotypes of F₁ and F₂ offspring depend on whether the recessive trait was expressed by the male or the female in the P₁ generation. With regard to Drosophila eye color, when the P₁ male expresses the white-eye phenotype and the female is homozygous red-eyed, all members of the F₁ generation exhibit red eyes. The F₁ females are heterozygous (X^WX^w), and the males are all X^WY, having received their X chromosome from the homozygous dominant P₁ female and their Y chromosome from the P₁ male.

A subsequent cross between the X^WX^w female and the X^WY male would produce only red-eyed females (with X^WX^W or X^WX^w genotypes) and both red- and white-eyed males (with X^WY or X^wY genotypes). Now, consider a cross between a homozygous white-eyed female and a male with red eyes. The F₁ generation would exhibit only heterozygous red-eyed females (X^WX^w) and only white-eyed males (X^wY). Half of the F₂ females would be red-eyed (X^WX^w) and half would be white-eyed (X^wX^w). Similarly, half of the F₂ males would be red-eyed (X^WY) and half would be white-eyed (X^wY).

X-Linked Recessive Disorders in Humans

Sex-linkage studies provided the fundamentals for understanding X-linked recessive disorders in humans, which include red-green color blindness and Types A and B hemophilia. Because human males need to inherit only one recessive mutant X allele to be affected, X-linked disorders are disproportionately observed in males. Females must inherit recessive X-linked alleles from both of their parents in order to express the trait.

Recessive Carriers

When they inherit one recessive X-linked mutant allele and one dominant X-linked wild-type allele, they are carriers of the trait and are typically unaffected. Carrier females can manifest mild forms of the trait due to the inactivation of the dominant allele located on one of the X chromosomes. However, female carriers can contribute the trait to their sons, resulting in the son exhibiting the trait, or they can contribute the recessive allele to their daughters, resulting in the daughters being carriers of the trait. Although some Y-linked recessive disorders exist, typically they are associated with infertility in males and are, therefore, not transmitted to subsequent generations.