INHERITANCE

For a very large percentage of human history, humans have been abysmally confused over matters concerning reproduction and inheritance. Some cultures did not relate conception to sexual intercourse at all and held that women alone were responsible for the genetic makeup of the child. In Western civilization, it was commonly held that only men contributed genetic information to the fetus while women provided the site for the fetus to develop. As for the inheritance of specific traits, a whole host of factors ranging from witchcraft to the imagination of the mother have been implicated, as evident in the following passages.


The ancients, who sought out the secrets of Nature… have taught of other causes for monstrous children and have referred them to the ardent and obstinate imagination that the mother might receive at the moment she conceived-through some object, or fantastic dream-of certain nocturnal visions that the man or woman have at the hour of conception. This is even verified by the authority of Moses (Chap. 30 [of Genesis]) when he shows how Jacob deceived his father-in-law Laban and enriched himself with his livestock by having rods barked and putting them in the watering trough, so that when the goats and ewes looked at these rods of various colors, they might form their young various colors: because the imagination has so much power over seed and reproduction that the stripe and character of them remain on the thing bred.
….Damascene, a serious author, attests to having seen a girl as furry as a bear, whom the mother had bred thus deformed and hideous, for having looked too intensely at the image of Saint John [the Baptist] dressed in skins, along with his [own] body hair and beard, which picture was attacked to the foot of her bed while she was conceiving.
Pare, 1573, p.38

The story of Marcus Damascene is well known, of the woman who gave birth to a child bristling with camel's hair for no other reason than that, in the act of procreation, she had gazed upon a picture of S. John the Baptist. It was for this cause that, when his niece had given birth to a somewhat hairy child, Pope Nicholas III by an edict ordered the removal of all the pictures in Rome.
…And it has been clearly enough shown that Demons are often visibly present to witches in one form or another. Therefore it should not seem wonderful that they at times give birth to children of such prodigious deformity* (refers to footnote which reads "For the question whether children can be generated by copulation with Incubus or Succubus devils see Gauzzo Copnedium Maleficarum. As this great authority says, there can be no doubt that a witch may bear a child from connexion with an Incubus devil, and all arguments to the contrary are vain and empty.")
Remy, 1595, p. 24-6

I have read that a citizen of Wittenburg was born with the face of a corpse. This happened because while his mother was carrying him in her womb, she suddenly came face to face with a dead body as she was walking along the road. At Eisenach, a chaste and very beautiful married woman gave birth to a dormouse because one of her neighbors had hung up a little bell for a particular dormouse, with the intention that its sound would drive other dormice away and this special dormouse ran up to the pregnant woman. She, taken by surprise, was so terrified at the sudden arrival and sight of the dormouse that the fetus in her womb degenerated into the shape of that little beast. During the pontificate of Nicholas III, a woman in one of the palaces in Rome gave birth to a child which looked like a bear. According to the doctors, this was because there were pictures of bears to be seen all over the palace. At Paderborn there was a famous case of a heretic woman, not quite sixteen years old, who gave birth to a son vested and tonsured like an ecclesiastic. Because of her violent hatred of Papists (as they call us), she was always cursing them to people she met while out walking. On the other hand, this may simply have been divine vengeance.
I now give further examples, drawn from other sources. I include cases of both maternal and paternal influence. Here is one relating to the mother. There was at Antwerp a pregnant woman who used to take delight in a monkey. She gave birth to a single daughter who exhibited many simian traits, such as hiding away, mimicking people, and things like that. There is an example relating to the father. Ludovico Del Rio, a man who enjoyed the highest esteem, faithfully accomplished a task for the King and for that reason was arrested by traitors during a full session of the Senate in Brussels. When his wife, who was pregnant at the time, saw the ring-leaders of the rebels bursting into her house, she was terrified out of her wits. After she had given birth, I baptized the child. Ever since birth the child has had its mother's terror in its panic-stricken eyes and even now, in adolescence, its loss of mind continues. Fernel wirtes in his hominis procreatione (On Human Procreation) that if you cover a pea-hen with pieces of white cloth while she is sitting on her eggs, she will produce chicks which are entirely white, not varied in color. Now surely no one maintains that eggs have nothing to do with the mother's body? So you see hereby the power of the imagination.
Jean Fernel, 16th century, from Maxwell-Stuart, p. 44

Stories were passed down that animals could give birth to offspring with human features after copulations between humans and animals. Below are drawings which were used to attest to the truth of this.
drawing drawing


For thousands of years people have been asking questions of how human traits are inherited. Although it has been long noted that individuals of a species produce offspring that pertain to that species and that offspring tend to resemble their parents, the precise mechanism was unknown. One popular belief was that little pieces of the organs of the body (called gemmules) broke off from their original organs and traveled to the gonads where they assembled into little people. Some of the first microscopists to look at sperm actually thought they saw a little person in the fetal position in the head of the sperm. (This belief helped to foster another belief-that masturbation and frequent sexual intercourse were debilitating to your health. It was argued that the more of these gemmules your body's organs lost, the more likely you would be to have poorer eyesight, go blind, get sick, develop arthritis, etc.)
Modern genetics began in the 1860s, when Gregor Mendel discovered the basis of heredity using pea plants in his garden. He had a number of strains of pea plants which varied in their height, flower color, seed texture, etc. Each strain was true breeding-while one strain always produced purple flowers, a second strain might always produce white flowers. The following cross is an example of the type of data he gathered.
1) The P (parental) generation:
Mendel crossed individuals from two different true-breeding strains, for example, he crossed a tall plant to a short plant


2) F1 generation (the first generation of offspring, the "children"):
Mendel observed that all the offspring were tall. It was obvious that offspring were not simply a "blend" of parental types as was commonly thought.

3) F2 generation (the "grandchildren"):
Mendel observed that the plants of this generation were mostly tall but some were short.


Mendel's insight involved the use of simple math: he observed F2 ratios of plants with certain traits such as 787 with one trait:277 with the other trait; 5,474:1,850; 651:207. All of these ratios are approximately 3:1 ratios. Such a ratio is possible if:
a) For each hereditary unit (gene), there are 2 alternate forms (alleles). One is dominant to the other (an individual with one dominant allele and one recessive allele will have the dominant trait). This was Mendel's Principle of Dominance.
b) Although organisms have 2 alleles of each gene, alleles separate during gamete formation so that each gamete only carries one allele. This was Mendel's Principle of Segregation.
c) Gametes from the two parents fuse at random.

Alleles (alternate forms of a gene) can be represented by letters. For example, a height gene responsible for the above cross might be represented with the letter T. The dominant and recessive allele might be represented by T and t. The genotype is the depiction of the alleles that an individual has:
--homozygous dominant: TT
--heterozygous: Tt
--homozygous recessive: tt
The phenotype is the outward appearance or the visible trait:
--dominant phenotype or recessive phenotype


RECESSIVE TRAITS IN HUMANS
Mendel's observations in pea plants are applicable to many traits in many organisms. Some traits have a recessive pattern of inheritance. The trait typically "skips generations" in that most children with the trait have parents without the trait. Two parents with the trait always have children with the trait and this trait is more likely to appear when parents are close relatives. The following pedigree depicts the transmission of a recessive trait (green) in three generations of a family. Tradition uses squares to represent males and circles to represent females.

pedigree
Some recessive traits in humans contribute to the diversity of human conditions which are considered normal such as attached earlobes, the inability to roll your tongue, blood type O, and the lack of hair on your middle digits of your fingers. Some recessive traits are harmful genetic diseases such as cystic fibrosis, Tay Sachs, phenyketonuria, albinism, galactosemia, xeroderma pigmentosum, and thalassemia.

DOMINANT TRAITS
There are many traits, in addition to those observed by Mendel, which display a dominant pattern of inheritance. At least one parent must be affected and 2 affected parents can have normal children.

pedigree
There are a number of dominant traits known in humans such as Widow's peak (in which a person's hairline forms a "V"), freely hanging earlobes, blood types A & B, mid-digital hair, and the ability to roll your tongue. Some dominant alleles cause genetic diseases such as Marfan syndrome, Alzheimer's disease, achondroplastic dwarfism, neurofibromatosis, Huntington disease, brachydactyly, and familial hypercholesterolemia.

Mendel's observations of dominant and recessive traits founded the science of genetics. Organisms as diverse as pea plants, humans, and fruit flies inherit traits according to the principles he observed. The two flies at the bottom of the following picture have mutant eye colors (brighter in the first and duller in the second compared to the normal eye color in the fly at the top of the image) which are recessive mutations.


The wrinkled wings in the fly above are caused by a dominant mutation.

There are however, some alleles which are inherited in ways other than those which Mendel described.
a) INCOMPLETE DOMINANCE
In incomplete dominance, neither allele is dominant and heterozygotes have a trait which is intermediate between that of the 2 homozygous conditions. In humans sickle cell anemia is the best known example of an incompletely dominant trait.- Homozygous recessive individuals have sickled red blood cells and heterozygotes normally don't have this condition but may develop it during times of stress.

b) CODOMINANCE
In codominance, heterozygotes aren't intermediates; they have both traits simultaneously. In
humans the best known example is that of the A and B glycoproteins which determine blood type. Heterozygotes express both conditions and are blood type AB.

c) MULTIPLE ALLELES
Although each individual may only have 2 alleles, there may be more than 2 types in a group of individuals. For example, in human blood groups there are 3 major alleles (A, B, O) and many minor ones; Rh blood groups have 8 common alleles and many rarer ones; MHC genes (which determine the "cellular fingerprint" used by the immune system to distinguish between self and nonself) have hundreds of alleles.

d) POLYGENIC INHERITANCE
A polygenic trait determined by several different genes so that there is no one gene which determines the trait by itself. Examples would include skin color, eye color, height, weight, & blood pressure. Obviously, the environment can also affect these traits

e) SEX LINKAGE:
As described previously, gender in humans is determined by the X and Y chromosomes. Males produces 2 types of sperm: one with an X, one with a Y. Which of these two types fertilizes the egg will determine the gender of the offspring. The Y is smaller than the X and doesn't carry alternate alleles for most genes on the X chromosome. As a result, males are more susceptible to mistakes on the X chromosome. Since they only have one copy of a gene and nothing to provide correct information if this one copy is bad. In humans color-blindness, muscular dystrophy, and hemophilia are sex linked traits. Although females may be affected by these traits, the majority of those affected are male.

The genetic mechanisms which function in these exceptions to Mendelian inheritance are also observed in many organisms other than humans. The ebony allele (bottom fly below) is incompletely dominant and heterozygotes have a pigmentation in between that of these two flies.

The yellow allele (the bottom fly in the first image) and the allele for white eyes are sex-linked mutations.
flies

CHROMOSOMAL MUTATIONS
Some human genetic disorders are not caused by individual genes but rather by problems with the number or structure of chromosomes. Normal humans have 46 chromosomes-23 kinds with two of each kind, one inherited from the mother, one from the father. The following karyotype is of a normal female wit 46 chromsomes.

karyotype
The following karyotype is of a normal male with 46 chromosomes. Note that the last pair of chromosomes (the X and Y) differ in size.


karyotype


A) CHANGE IN CHROMOSOME NUMBER--an unequal split (nondisjunction) during meiosis; humans normally have 46 chromosomes
1) aneuploidy: one chromosome too many or too few
a) In trisomy, there is one extra chromosome, for a total of 47 chromsomes in humans. The following image depicts the karyotype of an individual with Downs Syndrome, with 3 copies of chromosome 21. Most trisomies cause spontaneous abortions and only the trisomies of chromosome 21 or the sex chromosomes can permit an individual to live long past birth.

b) In monosomy, there is one chromosome too few, for a total of 45 chromosomes in humans. With the exception of women who only have one X chromosome (pictured below), monosomy is always lethal.
karyotype

2) polyploidy:
In polyploidy, there is a whole extra set of chromosomes are added. Trisomy in humans that would be equivalent to 46 chromosomes + 23 more for a total of 69. The most common cause of trisomy is that two sperm fertilize an ova. Rarely such an infant is born alive; those that are born alive do not survive long.

karyotype

B) CHANGE IN CHROMOSOME STRUCTURE
Some genetic problems are not caused by an abnormal number of chromosomes, but rather by changes in chromosome structure which can be classified as deletions, duplications, inversions, and translocations. For example, one of the chromosomes (the third chromosome) in the following karyotype has a deletion; it is missing a segment. The effects of these changes in chromosomal structure would depend on the chromosome affected and the genes contained in that region.

 

karyotype