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Chapter 15
HUMAN GENETICS
Human genetics studies inherited variation in humans.
To study other species geneticists
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Have standard stocks of genetically identical individuals, isogenic strains that are virtually
homozygous in all their loci.
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Conduct controlled matings.
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Raise the offsprings under carefully controlled conditions.
The study of human genetics requires alternative methods.
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Analysis of family pedigrees.
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Molecular studies.
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Studies of the karyotype.
Cytogenetics is the study of chromosomes and their role in inheritance.
Karyotype refers to the number of chromosomes of an individual and to the photomicrograph showing
the chromosomes.
ABNORMALITIES IN NUMBER OF CHROMOSOMES.
Abnormal chromosome number causes certain human disorders.
Polyploidy is the presence of several chromosome sets.
It is common in plants but rare in animals.
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Polyploidy is lethal in humans if it occurs in all cells of the body.
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A few triploid and tetraploid individuals have been born alive and survived a few days. They
were found to have a mixture of diploid and polyploid cells.
Aneuploidy is the presence or absence of a single extra chromosome.
It is more common in humans than polyploidy.
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Trisomic individuals have three chromosomes of a kind.
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Monosomic individuals have a single chromosome of a kind.
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Aneuploidy is due to abnormal mitosis or meiosis when the chromosomes fail to separate in the
anaphase. This is called nondisjunction.
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Down syndrome or trisomy 21 is the most common trisomy in humans.
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Kleinfelter syndrome, XXY, is a male with underdeveloped testes, enlarged breasts and one Barr
body per cell.
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Turner syndrome, XO, is an example of monosomy. The individual is a female with degenerate
ovaries, slight mental retardation, and webbed neck.
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Autosomal monosomy has not been seeing in live births. It probably results in the death of the
embryo at a very early stage.
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17% –20% of all pregnancies recognized at 8 weeks result in spontaneous abortion (miscarriage).
About have of these embryos have chromosome abnormalities. Autosomal monosomy is very
rare in embryos this old.
STRUCTURAL ABNORMALITIES OF CHROMOSOMES.
Translocation is the attachment of part of a chromosome to a nonhomologous chromosome.
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Nonhomologous chromosomes may exchange parts, reciprocal translocation.
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It may result in the elimination or duplication of genes.
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A type of Down syndrome results from the translocation of a portion of chromosome 21 to
chromosome 14. The individual has two normal chromosomes 21, one normal chromosome 14
and one abnormal chromosome 14 with a portion of chromosome 21 attached.
Deletions are loss of chromosomal material.
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A chromosome breaks and fails to rejoin.
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Most deletions are lethal.
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Cri-du-chat is due to a deletion in chromosome 5.
Fragile sites are weak points at specific sites in chromatids.
Part of a chromatid is attached by a thin portion of DNA
It occur at specific locations on both chromatids of a particular chromosome.
They have been identified in the X chromosome and certain autosomes.
In fragile X syndrome, the nucleotide triplet CGG is repeated 200 to 1000 times instead of the normal 50
times.
The effects of the fragile X syndrome range from mild learning disabilities to severe mental retardation.
AUTOSOMAL INHERITANCE
There are hundreds of enzyme defects caused by mutations of a single gene causing inborn errors of
metabolism.
Phenylketoneuria (PKU) is an autosomal recessive disorder in which toxic phenylketones damage the
developing nervous system.
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It converts phenylalanine to harmful phenylketones.
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It results in severe mental retardation during childhood.
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It can be treated with a modified diet low in phenylalanine during childhood.
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It may damage the fetus of women with PKU.
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More common in western Europeans and their descendants.
Sickle cell anemia is an autosomal recessive disorder in which abnormal hemoglobin is produced.
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It is caused by a single base difference in the hemoglobin gene resulting in the substitution of the
normal glutamine by a valine in hemoglobin.
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Valine is hydrophobic and make hemoglobin less soluble causing tiny crystals that deform the red
blood cell.
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The abnormal cells slow blood flow and blocks small blood vessels causing tissue damage.
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Individuals with the sickle cell gene are resistant to malaria.
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Common in persons of African descent: 1 in 12 African Americans.
Cystic fibrosis results from defective ion transport.
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This disorder is characterized by abnormal secretions in the body especially by the production of
viscous mucus in the respiratory tract.
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The heavy mucus also occurs in the ducts of the pancreas, liver and the intestines.
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It is the result of a mutation in the gene that codes for a protein that controls the transport of the
chloride ion across the cell membrane.
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Common in persons of European descent: 1 in 20 Americans is a heterozygous carrier.
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A severe form is found in northern Europe and a less severe form in southern Europe.
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Heterozygous individuals may be resistant to infectious diseases that cause diarrhea.
Tay-Sachs disease results from abnormal lipid metabolism in the brain.
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It is cause by an autosomal recessive that causes blindness and severe mental retardation.
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It results in death before the age of five.
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The lysosomes lack a lipid-digesting enzyme and brain cells are damaged by the accumulated
excess lipids.
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Common among Eastern European Jews.
Huntington disease is caused by a dominant autosomal gene.
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It results in muscle spasms, mental and physical deterioration beginning in middle age.
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It is caused by the abnormal repetition of the triplet CAG that codes for glutamine. The normal
gene repeats CAG 6 to 35 times while the mutant repeats the triplet 40 to 100 times.
Hemophilia A is an X-linked recessive disorder.
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It results in a defect in one of the components of blood required for clotting.
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It causes severe bleeding from the slightest wounds.
DIAGNOSIS
Some diseases can be detected before birth.
1. Amniocentesis is a technique used to sample the amniotic fluid, the fluid that surrounds the fetus.
The amniotic fluid contains cells that have been sloughed off the body of the fetus.
Cells found in the fluid are cultured and screened for genetic defects.
It is done in the second trimester of pregnancy.
The position of the fetus is determined by ultrasound imaging.
2. Chorionic villus sampling (CVS) is another technique that studies cells that have been removed
from the chrorion.
CVS provides results in the first trimester of pregnancy.
3. Genetic counselors can advise prospective parents with a family history of genetic disease about the
probabilities of having children with birth defects.
ABO BLOOD GROUPS
Human blood types is controlled by multiple alleles found in a single locus.
Alleles IA and IB code for a glycoprotein found on the surface of the red blood cell membrane.
Allele io does not code for the protein and is recessive to both IA and IB.
The glycoprotein is an antigen, a substance capable of stimulating the immune system.
Antigens are usually foreign chemicals that penetrate the body and cause an immune reaction.
Antibodies are proteins produced by the immune system to combine with antigen to inactivate the
antigen.
Rh FACTOR
Rh alleles control the expression of other red blood cell antigens.
There are eight different kinds of Rh antigens.
The most important is antigen D.
Rh-positive persons produce the antigen; Rh-negative do not produce the antigen.
Rh-negative persons do not produce antibodies unless they are exposed to Rh-positive blood. Then they
produce anti-D antibodies.
POLYGENES.
Quantitative traits show continuous variation such as height and skin color.
Quantitative traits are controlled by polygenes, many alleles in many loci.
Environmental factors are also involved in the expression of quantitative traits.
HUMAN GENOME PROJECT
It is an international undertaking to study the human genome in depth.
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Sequence of bases.
Gene mapping.
Discovery of unknown genes.
Function of “junk” DNA.
There are about 3 billion base pairs in the haploid genome.
About 95% of the DNA does not code for protein or its function is unknown.
Because most abnormal genes are recessive, they show phenotypically only in homozygous individuals.
Virtually every individual is heterozygous for several abnormal alleles.