Please Note:  There are two articles that are to accompany these notes. They could not be placed online due to copy-right laws. Please be sure to get these articles from your Instructor.
Titles:
"Double Mystery" by Lawrence Wright
and
"The Genetics of the Dunkers" by H. Bentley Glass
 

Course: NURS 3421 Basic Life Science
Instructor: Nancy Taggart Davis, Ph.D
Prerequisite: Anatomy, Physiology, Chemistry

Lecture Notes

Physical Basis of  Inheritance

Genes - small pieces of chromosomes. Control each specific cellular function. Responsible for ALL traits of organism. Occur in pairs. Derived in equal parts from mother and father.

Physical manifestations of gene action are dependent upon chemical reactions at cellular level. Genes code for protein.

genotype-gene construction of the individual.

phenotype observable characteristic resulting from the interaction of the environment on the genotype.

allele (allomorph) - the different, or alternate, form of a gene. Alleles that occur at the same position, or locus, on a chromosome pair may produce different effects during development.
 

homozygous - corresponding gene pairs produce same effect.

heterozygous - gene alleles produce different effects.
 

The Cell - each cell is a self sufficient unit. Each body (somatic) cell contains two sets of chromosomes - 2 sets of genes for each trait - these are found inside the NUCLEUS. The cell contains:

mitochondria - produces energy - ATPS

centrosome - necessary for cell division - help pull apart pairs of chromosomes.

ribosome - site of protein synthesis

endoplasmic reticulum - tubules to which ribsomes are attached. You see a lot of these in cells that produce a lot of protein such as pancreatic cells

Page 6

Chromosomes

Each, species has its own number, shape and size of chromosomes.

In man there are 23 pairs or 46.  Twenty-two (22) are autosomes, and 1 pair consists of two sex chromosomes.

female (.XX) male (XY)
 

diploid - double or two sets found in somatic cells. 46 chromosomes or 23 pairs

haploid - 1 set - found only in gametes. 23 chomosomes.

Each chromatid becomes 1 chromosome. In the dividing state chromosomes look like is:

All photographs of chromosomes are taken in the dividing state when gene replication has taken place.

Types of chromosomes:

metacentric - centromere in -middle
submetracentric - centromere near one end
acrocentric - terminally located centromere . Y appearance.

KARYOTYPE - chromosome analysis

Paired chromosomes are positioned in order of decreasing length. Each pair has a number. Pairs are put into 7 major groups.

Page 7

Cell Division

Mitosis - somatic cell division. Equal  division each daughter cell has exactly the
 same kind and number of chromosomes as the mother cell.

STAGES OF MITOSIS

Prophase - chromosomes become visible and begin to migrate toward middle of cell. Centrosome divides and each half moves to opposite sides. Nuclear membrane disintegrates. BY THIS POINT DNA REPLICATION HAS OCCURRED.

Metaphase - nuclear membrane disappears. Chromosomes are at their thickest and shortest and are lined up in the center of the cell.

Anaphase- chromatids separate and migrate to opposite poles.

Telophase - nuclear membrane forms around 2 sets of chromatids.

Interphase - protein synthesis takes place.

Meiosis - (to make smaller) - germ cell duplications. Reduces number of chromosomes to half (26) so that when two germ cells unite they contain the full number of chromosomes (46). Meiosis occurs only in the testes and ovaries.

Meiosis I --first DNA replicates itself, the pairs of chromatids line up in
 homologous pairs 4 chromatids are intimately associated at this
 stage and this is when crossing over takes place. During the first
 division the chromatids do not separate as in mitosis. The
 homologous chromatid pairs separate from each other and migrate
 to opposite ends of the dividing cell. Maternally and paternally
 derived chromosomes are distributed in a random fashion.
 Cell division continues and we now have two cells with half the
 number (23) of chromosomes.

Meiosis II --This is an equal division. Here the two chromatids separate. No DNA replication takes place during Meiosis II, The complexity of meiosis makes it susceptible to faulty division.

The mechanism behind spermatogenesis and oogenesis are similar except that spermatogenesis results in 4 gametes, 2 with X and 2 with Y chromosomes and cogenesis in only one gamete (due to polar body formation) with an X chromosome. In females all DNA replication occurs during -intrauterine life and -remains at that state until puberty. Unequal cytoplasmic division and polar body formation is necessary in the female to produce a large egg with lots of cytoplasm which aids the embryo during early development.

Page 8.

Some characteristics might be inherited through maternal cytoplasm.

Ovaries contain approximately 400,000 primary oocytes. Hormones initiate first meiotic division.

Linkage and Crossing Over

Linkage --when two traits often occur together such as color blindness and hemophilia or in mice, for example, coat color and emotionality, the two genes are close together on the chromosome and usually cross over together.

Crossing over --occurs during meiosis. Increases amount of variation. Pairs of homologous chromatids line up. They get so close that parts of chromatid touch each other. Points of contact are chiasma. Some genes break off and join the other chromosome And vice versa.

Chemical Basis of Heredity -- Chromosomes are made up of DNA.

A gene is a section of a chromosome that codes the information to produce an enzyme or a structural protein.
 

DNA - 2 functions
1) duplication

2) production of protein

DNA - made up of four (4)nucleotides which contain sugar (deoxyribose) phosphate and a nitrogenous base-purines - (1) adenine and (2) guanine (3)cytosine and (4)thymine. binding always takes place like this: adenine-thymine quanine-cytosine

The sequence of bases - AGTTCAC is the genetic code.

RNA - similar to DNA but the sugar is ribose and thymine is replaced with uracil. RNA is single stranded. RNA is necessary for protein synthesis.

Genetic Code.- 20 known amino acids (aa). 3 bases represent 1 amino acid this is called a codon. More than one triplet can code for the same amino acid.

Page 9

Amino acids make polypeptide chains. Polypeptide chains make up proteins.

Protein Synthesis
DNA- transcription- RNA translation
     \----------------->messenger------------>Protein
      occurs on ribosome used transfer RNA
      which are attached to aa.

Three types of RNA

1) messenger-transcribed from DNA, link between chromosomes and
 ribosomes, template for protein.
2) transfer-transfers aa - to messenger RNA

3) ribosomal-translation takes place on ribosome

 The amino acids (aa) are just floating around on the cytoplasm. We
 get most of them from our diet and the break down of body protein.
 Our body produces half from C,O,H,N and the rest are essential.

Control of  Gene Action

1) amino acid sequence (structural genes)

2) controlling role - allows some genes to be active- while others are inactive:
 

Operator -- initiate activities of structural genes.

Regulator genes -- controls operator genes - makes repressor substance.
presence of repressor substance there is no enzyme and structural protein formation.
viruses cancer, etc. might elicit their effect via regulator genes also refered to as oncogenes.

Mutation --refers to a change in genetic material.

Page 10

Gene Transmission in Families

Great variety to genetic disorder

some occur at birth - other in adulthood - severity of disorders vary.

Hereditary - transmitted from one generation to next

Congenital - present at birth - can be due to hereditary or environmental causes

Principles of Inheritances

Laws of gene activity - statistically predictable - mendelian ratios

Principles of Dominance

2 genes for each trait - there is competition between the 2 genes for expression of

trait.

Dominant Trait- the characteristic that is seen - manifested.

Recessive Trait -the hidden trait must be tgmazygnus to be expressed.

Phenotype - dominant characteristic - what is seen.

Genotype - usually impossible to tell.whether it is homozyous or heterozygous.
 

Principle of Segregation - The separation of gametes during meiosis and their
recombination during fertilization. A mixing of genetic material. When a homozygous
dominate trait mixes with a homozygous recessive trait, the first generation all appear
to display the dominate trait. The phenotype is dominate, but the genotype is
heterozygous. When 2 heterozygous parents mate the offspring normally consists of
3 dominate traits and I recessive, 3:1 ratio. What would be the genotype ratio?

Chance -- determines which gene will travel to which gamete.

  Page 11

Principles of Independent Assortment

Living things have-more than one trait. Each trait can have two forms. When these traits are assorted into gametes they do it in a manner independent of each other. For example if each parent is heterozygous for sickle cell anemia and hemophilia they could produce four possible phenotypes in their children.

1. Normal

2. Sickle cell anemia child without hemophilia

3. Hemophilic child without sickle cell

4. Child having both sickle cell and hemophilia
 
 

The following is an example of how this occurs.

Each parent has the following genotype:

Trait for
normal shape-------S s H h --------trait for hemophilia
(small "s" representing the trait for Sickle Cell and "H" representing trait for normal clotting of blood)

A gamete only contains one gene for each trait. Therefore each parent can make the following gametes:

SH Sh SH sh

You can figure out the gametes out like this:
         H      h

S      SH    Sh

s      SH     sh

Page 12

The traits  appear in individual gametes. Each combination has an equal chance of forming (independent assortment).

When the egg becomes fertilized, two gametes come together. Again, chance
determines which two gametes comes together, but there is a greater chance for
some phenotype combinations than others. The following is a schematic way of
estimating which combinations will occur most frequently:

                                               (female)
                            SH         Sh          sH         sh
   (male)     SH   SSHH     SSHh    SsHH     SsHh     all normal
                 Sh    SSHh      Sshh      SsHh      Sshh   2 normal; 2  w/hemophilia
                 sH    SsHH     SsHh      ssHH     ssHh      2 w/sickle cell
                 sh     SsHh      Sshh      ssHh       sshh       1H, 1SC, 1 w/both
This is called a punnet square
There are 16 possible genotypes of the fertilized eggs
 

Ratio of phenotypes 9:3:3:1

How many different genotypes would there be?

Inheritance Models You should be able to figure out the possible genotypes and phenotypes for offspring from the following combinations:

1. Homozygous parents for similar trait. 2. One parent homozygous dominate, one parent homozygous recessive. 3. Both parents heterozygous for a trait. 4. One parent heterozygous, one parent homozygous.

Pedigree Chart   (Family Tree)  (refer drawing to understand the following):

Page 13.

Proband refers to the affected person. When making a pedigree chart you begin with the proband.

-consaguineous marriage--is marriage is represented by a double bar between the siblings. Arabic numbers are used in order of birth. Generations are represented by roman numerals, earliest at top. Normal spouses are often omitted.

Terms relating to the Single Mutant Gene

Autosomal trait - trait determined on the autosome. May be dominant or recessive.

Sex-linked - trait is on one of the sex chromosomes, may be dominant or recessive.

Structural defect - usually the result of an abnormal dominant gene.

Inborn errors of metabolism - usually a recessive inheritance pattern.

Dominant traits - more frequent, usually less severe than recessive traits.

Double dose effect - 2 abnormal gene - seen with 2 abnormal dominate genes or 2
abnormal recessive genes. The presence of a normal gene reduces the severity of the
disorder.

Lethal - zygote dies in utero - can not be passed on to subsequent generations.

Semilethal - individual dies at an early age.

Recessive trait - one abnormal gene that can be passed on through many generations without being detected. You need two recessive genes for trait to be present in the phenotype.

Generalizations relating  to Autosomac Inheritance

44 autosomes. Majority of disorders are autosomal. Why? Displayed with equal frequency in males and females. Why?

Generalizations of Autosomal - dominant Inheritance

Trait expressed in both homozygous and heterozygous.
Presence of gene is always expressed in phenotype.
Easily traced through generations - positive family history.
Individual with autosomal dominant disorder will always have effected parent unless he/she is a fresh mutation.
Trait usually only occurs in one parent.
Trait appears equally in both sexes.

Page 14

Rarely appears in homozygous state - if it does, all offspring are affected. Double dose effect Normal children of affected parent cannot transmit trait. Whv?
Age at which trait is manifested determines survival of severe dominant trait, example:
Huntington's Chorea, Joseph's Disease. Why? Lethal disease which kill before
reproduction occurs are not transmitted.

Generalizations of Autosomal - Recessive Inheritance

In order for trait to appear, the gene pair must be homozygous for the-disorder. Most
people heterozygous for a recessive trait go undetected in the population. It is felt that
most people carry some potential lethal or semilethal genes (3-8).

Negative Family History - no evidence of trait in previous generations.

Disorders can result from new mutations or from mating of parents heterozygous for the
trait (25% of children will have the disease while 50% will be unaffected carriers). If one
parent is affected and one is homozygous normal, all offspring will be heterozygous for
the trait (carriers). There is no sex difference. The heterozygous state can usually be
detected by biochemical testing methods.

Intermediate inheritance - (incompletely dominate or incompletely recessive) is between dominant and recessive. The gene is partially expressed in the heterozygote.

Inheritance pattern is same as autosomal - recessive. Severely affected is always. homozygous. Examples: sickle-cell, thalassemia.

Codominance - Both alleles of a gene pair are equally expressed. Example - ABO Blood groups - expressed as 6 possible gene combinations A/A, B/B, 0/0, A/0, B/0, A/B. A + B are dominate over 0 but condominate to each other.

Generalizations of Sex-Linked Inheritance

Inheritance pattern will vary according to sex.

2 X chromosomes are homologous and act as autosomes with 2 genes at each locus. X and Y chromosomes are not homologous.

3 types of sex linked transmissions:

1. genes carried on the X chromosome exclusively

2. genes are carried only on the Y chromosome

Page 15

3. genes occur at paired loci on both the Y and X (questionable as to whether this occurs in man)

Genes on Y (Y linked) are responsible for male phenotype. They carry no medically significant genes.

X chromosome carries 60-70 traits. Genes on the X chromosome have no counterpart on the Y chromosome.

Females (XX) are either heterozygous or homozygous for a trait. Males (XY) have only one gene for the trait on the Y and the X chromosome (hemizygous). Traits determined on the X gene are always expressed in males. X linked is referred to as sex-linked. No father to son transmission! Why?

X linked Dominant Inheritance

Unusual type of inheritance; very rare i.e. D - resistant rickets. Resembles autosomal
dominate disorders (positive family history), but affected male transmits disease to all of
his daughters and none of his sons. Why? Affected female transmits to half daughter
and half sons. The effects are more severe in males because females having one
normal gene.

X linked Recessive Inheritance
Most common type of sex linked. Hemophilia, hydrocephalus, diabetes-insipidus, Duchenne-type muscular dystrophy. Behaves as any recessive gene. In the male, who has only one X, the abnormal trait will always be apparent. Male can not transmit disease to his sons. Transmits the gene to all his daughters who will be carriers. Heterozygous females will transmit gene to half her sons and half her daughters. Females with the disease are no more severely affected than males because of X inactivation (you would think that they would be because of the double dose effect).
 

Sex-Related Gene Expression

Sex-influenced - autosomal trait that is expressed more frequvently in one sex. For example, men get their mothers gene for breast size and shape but they usually do not express it ; the can pass the gene on to their daughters whom can express the trait. Sex-limited - only one sex is affected - these traits are seen more frequently in the male - probably influenced by testicular hormone - gout, baldness. In males the trait behaves as an autosomal-dominant. In females as a autosomal-recessive. Men who secrete testosterone behave as autosomal dominates. Sex-limited traits are difficult to distinguish from X-linked recessives by the pedigree pattern.

Continue on document 2
Please close this document and return to:
http://loki.stockton.edu/~davisn/geneticsindex.html
Choose option #2 under "Lecture Notes" to continue..............