Human Genetics

1. Objectives and Reading Guide

2. Vocabulary Defined

Vocabulary

autosomes

The chromosome other than the sex chromosomes.

carrier

A person who is heterozygous for a recessive genetic disorder; the person does not have the disease but can pass the disease allele to the next generation.

sex-linked trait

A trait that is due to a gene located on a sex chromosome, usually the X-chromosome.

3. Introduction

Introduction

You might know someone who was born with a genetic disorder, such as cystic fibrosis or Down Syndrome. And you might have wondered how someone inherits these types of disorders. It all goes back to Mendel! Mendel’s rules laid the foundation for understanding the genetics of all organisms, including humans. We can apply Mendel’s rules to describe how many human traits and genetic disorders are inherited. Some disorders are caused by a recessive allele, while other disorders are caused by a single dominant allele. Therefore, we can draw a Punnett square to predict the number of offspring that may be affected with these diseases, just like we predicted for other traits in the previous lessons. Since Mendel’s time, we have also expanded our knowledge of inheritance and understand that genes are located on chromosomes. Now we can now explain special inheritance patterns that don’t fit Mendel’s rules.

4. Sex-Linked Inheritance

Sex-linked Inheritance

What determines if a baby is a boy or a girl? Recall that you have 23 pairs of chromosomes, one pair of which are the sex chromosomes. Everyone has two sex chromosomes, X or Y, that determine our sex. Females have two X chromosomes, while males have one Y chromosome and one X chromosome. So if a baby inherits an X from the father and an X from the mother, it will be a girl. If the father’s sperm carries the Y chromosome, it will be a boy. Notice that a mother can only pass on an X chromosome, so the sex of the baby is determined by the father. The father has a 50 percent chance of passing on the Y or X chromosome, hence it is a 50 percent chance whether a child will be a boy or a girl.

One special pattern of inheritance that doesn’t fit Mendel’s rules is sex-linked inheritance, referring to the inheritance of traits which are due to genes located on the sex chromosomes. The X chromosome and Y chromosome carry many genes and some of them code for traits that have nothing to do with determining sex. Since males and females do not have the same sex chromosomes, there will be differences between the sexes in how these sex-linked traits are expressed.

One example of a sex-linked trait is red-green colorblindness. People with this type of colorblindness cannot distinguish between red and green and often see these colors as shades of brown (Figure below). Boys are much more likely to be colorblind than girls. That’s because colorblindness is a sex-linked recessive trait. Boys only have one X chromosome, so if that chromosome carries the gene for colorblindness, they will be colorblind. As girls have two X chromosomes, a girl can have one X chromosome with the colorblind gene and one X chromosome with a normal gene for color vision. Since colorblindness is recessive, the dominant normal gene will mask the recessive colorblind gene. For a girl to be colorblind, she would have to inherit two genes for colorblindness, which is very unlikely. Many sex-linked traits are inherited in a recessive manner.

A woman can be a carrier of colorblindness, however. A carrier appears normal but is capable of passing on a genetic disorder to her child. Carriers for colorblindness have a heterozygous genotype of one colorblind allele and one normal allele. We can use a Punnett square to predict the probability of a carrier passing on the trait to her children. For example, if a woman who is a carrier for colorblindness has children, her boys would have a 50% chance of being colorblind and her girls have a 50% chance of being carriers.

5. Human Genetic Disorders

Human Genetic Disorders

Some human genetic disorders are also X-linked or Y-linked, which means the faulty gene is carried on these sex chromosomes. Other genetic disorders are carried on one of the other 22 pairs of chromosomes; these chromosomes are known as autosomes or autosomal chromosomes.

Some genetic disorders are caused by recessive or dominant alleles of a single gene on an autosome. These disorders would then have the same inheritance pattern as any other dominant or recessive trait. An example of an autosomal recessive genetic disorder is cystic fibrosis. Children with cystic fibrosis have excessively thick mucus in their lungs which makes it difficult for them to breathe. The inheritance of this recessive allele is the same as any other recessive allele, so a Punnett square can be used to predict the probability that two carriers of the disease will have a child with cystic fibrosis.

Another recessive trait that we mentioned previously was sickle cell anemia. A person with two recessive alleles for the sickle cell trait (aa) will have sickle cell disease. In this disease the hemoglobin protein is formed incorrectly and the person’s red blood cells are misshapen. A person who does not carry the sickle trait has a homozygous dominant genotype (AA). Remember the trait showed incomplete dominance, so a person who is heterozygous for the trait (Aa) would have some sickle-shaped cells and some normal red blood cells.

You can also use a simple Punnett square to predict the inheritance of a dominant autosomal disorder, like Huntington’s disease. If one parent has Huntington’s disease, what is the chance of passing it on to their children? If you draw the Punnett square, you will see that there is a 50 percent chance of the disorder being passed on to the children. Huntington’s disease causes the brain’s cells to break down, leading to muscle spasms and personality changes. Unlike most other genetic disorders, the symptoms usually do not become apparent until middle age.

Genetic diseases can also be carried on the sex-chromosomes. An example of a recessive sex-linked genetic disorder is hemophilia. A hemophiliac’s blood does not clot, or clots very slowly, so he or she can easily bleed to death. As with colorblindness, males are much more likely to be hemophiliacs since the gene is on the X chromosome. Because Queen Victoria of England was a carrier of hemophilia, this disorder was once common in European royal families. Several of her grandsons were afflicted with hemophilia, but none of her granddaughters were affected by the disease, although they were often carriers. Because at the time medical care was very primitive, often hemophiliacs bled to death, and usually at a young age. Queen Victoria’s grandson Frederick died at age 3, and her grandson Waldemar died at age 11 (Figure below).

Many genetic disorders are recessive, meaning that an individual must be homozygous for the recessive allele to be affected. Sometimes these disorders are lethal (deadly), however, heterozygous individuals (unaffected individuals with one dominant allele and one recessive allele) survive. This allows the allele that causes the genetic disorder to be maintained in a population's gene pool. A gene pool is the complete set of unique alleles in a species or population. A mutation is a change in the DNA sequence. New mutations are constantly being generated in a gene pool.

6. Pedigree Analysis

Pedigree Analysis

A pedigree is a chart which shows the inheritance of a trait over several generations. A pedigree is commonly created for families, and it outlines the inheritance patterns of genetic disorders. Figure below shows a pedigree depicting recessive inheritance of a disorder through three generations. Scientists can tell the genetics of inheritance from studying a pedigree, such as whether the trait is sex-linked (on the X or Y chromosome) or autosomal (on a chromosome that does not determine sex), whether the trait is inherited in a dominant or recessive fashion, and possibly whether individuals with the trait are heterozygous or homozygous.

7. Chromosomal Disorders

Chromosomal Disorders

Some children are born with genetic defects that are not carried by a single gene. Instead, an error in a larger part of the chromosome or even in an entire chromosome causes the disorder. Usually the error happens when the egg or sperm is forming. One common example is Down syndrome (Figure below). Children with Down syndrome are mentally disabled and have collection of recognizable physical deformities. Down syndrome occurs when a baby receives an extra chromosome from one of his or her parents. Usually a child would have one chromosome 21 from its mother and one chromosome 21 from its father. But in an individual with Down syndrome, there are three copies of chromosome 21. Down syndrome is therefore also known as Trisomy 21.

Another example of a chromosomal disorder is Klinefelter syndrome, in which a male inherits an extra “X” chromosome. These individuals have underdeveloped sex organs and elongated limbs, and have difficulty learning new things. Outside of chromosome 21 and the sex chromosomes, most embryos with extra chromosomes do not even make it to the fetal stage. Because chromosomes carry many, many genes, a disruption of a chromosome potentially causes severe problems with development of the fetus.

Besides diseases caused by duplicated chromosomes, other chromosomal disorders occur when the structure of a chromosome is disrupted. For example, if a tiny portion of chromosome 5 is missing, the individual will have cri du chat (cat’s cry) syndrome. These individuals have misshapen facial features and the infant’s cry resembles a cat’s cry.

8. Lesson Summary

Lesson Summary

• Some human traits are controlled by genes on the sex chromosomes.
• Human genetic disorders can be inherited through recessive or dominant alleles, and they can be located on the sex chromosomes or autosomes.
• Changes in chromosome number can lead to disorders like Down syndrome.