1. Mendel and the Gene Idea
Chapter 14

2. Points to Ponder
What is the genotype and the phenotype of an individual?
What are the genotypes for a homozygous recessive and dominant individuals and a heterozygote individual?
Be able to draw a punnett square for any cross (1-trait cross, 2-trait cross and a sex-linked cross).
What are Tay-Sachs disease, Huntington disease, sickle-cell disease, and PKU?
How are each of the above inherited?
What is polygenic inheritance?
What is a multifactorial trait?
What is sex-linked inheritance?
Name 3 X-linked recessive disorders.
What is codominance?
What is incomplete dominance?
What do you think about genetic profiling?

3. Gregor Mendel ( )
Documented a particulate mechanism of inheritance through his experiments with garden peas
Figure 14.1

4. “particulate” inheritance
Mendel thought that parents pass on discrete heritable units, “genes” (Mendel referred to these as “factors”)

5. Mendel’s experiments
Concept 14.1: Mendel used the scientific approach to identify some basic Laws of Inheritance
Mendel discovered the basic principles of heredity by breeding garden peas in carefully planned and executed experiments

6. Some genetic vocabulary
Gene: the basic unit of heredity in a living organism; a gene is a section of a chromosome that codes for a trait, or characteristic.
Alleles: alternate forms of a specific gene at the same position (locus) on a gene (e.g. allele for unattached earlobes and attached lobes); alleles occur in pairs

7. For each character,
An organism inherits two alleles, one from each parent
A genetic locus is actually represented twice, in diploid organisms
Homologous chromosomes, one paternal, one maternal 
Figure 14.4
Allele for purple flowers
Locus for flower-color gene
Homologous
pair of
chromosomes
Allele for white flowers
Homologues are similar in size, centromere location, and in the genes that they carry

8. Dominants and Recessives
If the two alleles at a locus differ
Then one, the dominant allele, determines the organism’s appearance
The other allele, the recessive allele, has no noticeable effect on the organism’s appearance (is “masked”)

9. Vocabulary review
Homozygous: (aka “purebred” or “true-breeding”) have an identical set of alleles for a trait Heterozygous: hybrid; nonmatching alleles

10. Understanding genotype & phenotype
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Genotype – specific genes for a particular trait written with symbols (example: EE, Ee, or ee)
Phenotype – the physical or outward expression of the genotype
egg E e E E e e
sperm
fertilization
zygote EE ee Ee
growth and
development EE ee Ee
unattached earlobe
attached earlobe
unattached earlobe
Allele Key
E= unattached earlobes
e= attached earlobes

11. Mendel’s Experimental, Quantitative Approach
Mendel chose to work with peas
Because they are available in many varieties
Because he could strictly control which plants mated with which

12. He started his experiments with varieties that were “true-breeding” (purebred lines isolated through self-pollination) = “P” generation
When Mendel crossed contrasting, true-breeding white and purple flowered pea plants
ALL of the offspring (F1 generation) were purple. Why?

13. Punnett Squares tutorial
The Punnett square is a diagram that is used to predict an outcome of a particular cross or breeding experiment. It is named after Reginald C. Punnett, who devised the approach, and is used by biologists to determine the probability of an offspring having a particular genotype.

14. Mendel’s Principle of Dominance and Recessiveness
Mendel reasoned that
In the F1 plants, only the purple flower “factor“ was affecting flower color (phenotype) in these hybrids
Purple flower color was dominant, and white flower color was recessive
In such cases, the dominant allele “MASKS” the recessive

15. Next, when Mendel crossed the purple F1 plants:
WHAT DO YOU PREDICT THE COLOR RATIOS WOULD BE FOR THE F2 GENERATION?
Mendel found that most of the F2 plants had purple flowers, but some had white flowers
He found a repeatable ratio of about 3:1, purple to white flowers, in the F2 generation

16. Mendel observed the same pattern in many other pea plant characters 
Table 14.1
Mendel observed the same pattern in many other pea plant characters 
Mendel developed a hypothesis to explain the 3:1 inheritance pattern that he observed among the F2 offspring

17. The Law of Segregation
The two alleles for a heritable character separate (segregate) during gamete formation and end up in different gametes

18. Segregation of Alleles (meiosis)
Does Mendel’s segregation model account for the 3:1 ratio he observed in the F2 generation of his numerous crosses?

19. The Law of Independent Assortment
Each pair of alleles segregates independently during gamete formation
Animated version:

20. Possible gametes for TWO traits

21. Crossing over prior to gamete formation increases variables
Sex and variation
Crossing over prior to gamete formation increases variables
Independent assortment
Crossover animation

22. The extent of variation
Not only does meiosis guarantee segregation and independent assortment of alleles, but crossing over also mixes up alleles on homologous chromosomes before distribution
“Therefore, in humans with 23 pairs of chromosomes, a gamete (egg or sperm) could have 223 or 8,388,604 possible combinations of chromosomes from that parent. Any couple could have 223 × 223 or 70,368,744,177,644 (70 trillion) different possible children, based just on the number of chromosomes, not considering the actual genes on those chromosomes.
Thus, the chance of two siblings being exactly identical would be 1 in 70 trillion.
In addition, something called crossing over, in which the two homologous chromosomes of a pair exchange equal segments during synapsis in Meiosis I, can add further variation to an individual’s genetic make-up.”

23. Dihybrid Crosses & Independent Assortment of alleles
Illustrates the inheritance of two characters
Produces four phenotypes in the F2 generation

24. The reality of inheritance
Concept 14.3: Inheritance patterns are often more complex than predicted by simple Mendelian genetics
The relationship between genotype and phenotype is rarely simple
What about green eyes? Hazel eyes?

25. The genetics of eye color
At one locus (site=gene) there are two different alleles segregating: the B allele confers brown eye color and the recessive b allele gives rise to blue eye color.
At the other locus (gene) there are also two alleles: G for green or hazel eyes and g for lighter colored eyes.
The B allele will always make brown eyes regardless of what allele is present at the other locus. In other words, B is dominant over G. In order to have true blue eyes your genotype must be bbgg. If you are homozygous for the B alleles, your eyes will be darker than if you are heterozygous and if you are homozygous for the G allele, in the absence of B, then your eyes will be darker (more hazel) that if you have one G allele.

26. Extending Mendelian Genetics for a Single Gene
The inheritance of characters by a single gene
May deviate from simple Mendelian patterns
Exceptions to the “rules” are listed in the following slides
Need practice? Try these “drag and drop” Punnett squares

27. The Spectrum of Dominance
Complete dominance
Occurs when the phenotypes of the heterozygote and dominant homozygote are identical PP pp Pp

28. Incomplete dominance (aka “blended inheritance)
The phenotype of F1 hybrids is somewhere between the phenotypes of the two parental varieties
Example: Flower colors
RR = red
R’R’ = white
RR’ = pink (intermediate pigmentation)

29. The Spectrum of Dominance
In codominance
Two dominant alleles both affect the phenotype in separate, distinguishable ways
IAIB = The human blood group type AB is an example of codominance
RW = roan coat color in cattle or horses

30. Multiple Alleles and Codominance
Most genes exist in populations
In more than two allelic forms
Table 14.2
The ABO blood group in humans
Is determined by multiple alleles

31. Frequency of Dominant Alleles
Are not necessarily more common in populations than recessive alleles
It really depends on whether a trait gives an individual an adaptive advantage, and is naturally selected.
Examples: type O blood (ii) recessive present in majority of population

32. Pleiotropy
Pleiotropy describes the genetic effect of a single gene on multiple phenotypic traits.
The underlying mechanism is that the gene codes for a product that is, for example, used by various cells, or has a signaling function on various targets.
A classic example of pleiotropy is the human disease PKU (phenylketonuria).
This disease can cause mental retardation and reduced hair and skin pigmentation, and can be caused by any of a large number of mutations in a single gene that codes for the enzyme (phenylalanine hydroxylase), which converts the amino acid phenylalanine to tyrosine, another amino acid.
Depending on the mutation involved, this results in reduced or zero conversion of phenylalanine to tyrosine, and phenylalanine concentrations increase to toxic levels, causing damage at several locations in the body.
PKU is totally benign if a diet free from phenylalanine is maintained.

33. Which of Mendel’s Laws does this defy? See linkage animation
Gene Linkage
Sometimes, when genes are located close together on the same chromosome, they tend to be inherited together.
Which of Mendel’s Laws does this defy?
See linkage animation
A “classic” example of this is why cats with white fur and blue eyes are (more often than not) also deaf.

34. Extending Mendelian Genetics for Two or More Genes
Many traits (especially in complex organisms)
May be determined by two or more genes (polygenic)
In EPISTASIS “standing upon”
the phenomenon where the effects of one gene are modified by one or several other genes (which are sometimes called modifier genes).
A gene at one locus alters the phenotypic expression of a gene at a second locus

35. An example of epistasis in mice
Here we see the effect the bb gene combo has on the C gene for the agouti (brownish) fur color in mice
cc combo = white fur
C_ combo = black fur,
unless bb “stands upon” it. Then you get agouti color. BC bC Bc bc
1⁄4
BBCc
BbCc
BBcc
Bbcc
bbcc
bbCc
BbCC
bbCC
BBCC
9⁄16
3⁄16
4⁄16 
Sperm
Eggs
Figure 14.11

36. Other variations in gene expression
Incomplete Expressivity is seen in cases where individuals with the same genotypes may have, often for unknown reasons, variability in their phenotypes.
This is often seen in genetic diseases where one person with a disease such as diabetes may be very severely effected while another with the same allele may have a milder form of the disease.
Incomplete Penetrance is seen when an individual with a particular genotype does not express the phenotype. Again the reasons for this are not clearly understood.
For example, known mutations in the gene responsible for Huntington disease have “95% penetrance”, because 5% of those with the dominant allele for Huntington disease don't develop the disease and 95% do.

37. Beyond simple inheritance
Polygenic traits - two or more sets of alleles govern one trait
Each dominant allele codes for a product so these effects are additive
Results in a continuous variation of phenotypes
e.g. skin color ranges from very dark to very light
Note that: Environmental effects can cause intervening phenotypes! 
AaBbCc
aabbcc
Aabbcc
AaBbcc
AABbCc
AABBCc
AABBCC
20⁄64
15⁄64
6⁄64
1⁄64
Fraction of progeny

38. Polygenic inheritance
Multifactorial trait – a trait that is influenced by both genetic and environmental factors
e.g. skin color is influenced by sun exposure
e.g. height can be affected by nutrition
most
are
this
height
Number of Men
few
few 62 64 66 68 70 72 74
short
tall
Height in Inches
Courtesy University of Connecticut/Peter Morenus, photographer;

39. Genes are affected by Environment
While there is a strong genetic component in human height, the average height has increased over the past 50 years in developed countries. This is considered to be due to improved nutrition.
Likewise, a cotton plant may have the alleles necessary for high yields but if it doesn't receive enough water or fertilizer it cannot reach its genetic potential.

40. Example:
A phenotypic range of a particular genotype may be influenced by the environment
Figure 14.13
Exact color often mirrors the pH of the soil; acidic soils produce blue flowers, neutral soils produce very pale cream petals, and alkaline soils results in pink or purple. This is caused by a color change of the flower pigments in the presence of aluminum ions which can be taken up into the flower.

41. Demonstrating environmental influences on phenotype
Beyond simple inheritance
Demonstrating environmental influences on phenotype
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Himalayan rabbit/Siamese cat coat color influenced by temperature
There is an allele responsible for melanin production that appears to be active only at lower temperatures
The extremities have a lower temperature and thus the ears, nose paws and tail are dark in color
© H. Reinhard/Arco Images/ Peter Arnold

42. Humans are not convenient subjects for genetic research. Why?
Many human characters
Vary in the population along a continuum and are called “quantitative characters”
Humans are not convenient subjects for genetic research. Why?
However, the study of human genetics continues to advance
Advances in personal genomic testing

43. A pedigree
Is a family tree that describes the interrelationships of parents and children across generations
Inheritance patterns of particular traits can be traced and described using pedigrees Ww ww WW or
First generation
(grandparents)
Second generation
(parents plus aunts
and uncles)
Third
generation
(two sisters) Ff ff
FF or Ff FF
Widow’s peak
No Widow’s peak
Attached earlobe
Free earlobe
(a) Dominant trait (widow’s peak)
(b) Recessive trait (attached earlobe)

44. Genetic mutations can lead to familial diseases
Somatic mutations — such as in skin cells as a result of sun exposure — tend to accumulate over the course of our lives, but are not typically passed on to children.
But other errors can occur in the DNA of cells that produce the eggs and sperm. These are called germline mutations and can be passed from parent to child.
If a child inherits a germline mutation from their parents, every cell in their body will have this error in their DNA.
Germline mutations are what cause diseases to run in families, and are responsible for hereditary diseases.

45. (this is how the code should read)
How does it work?
A gene is essentially a sentence made up of the bases A, T, G, and C that describes how to make a protein.
Any changes to those instructions can alter the gene's meaning and change the protein that is made, or how or when a cell makes that protein.
There are many different ways to alter a gene, just as there are many different ways to introduce typos into a sentence. In the following examples of some types of mutations, we use the sentence to represent the sample gene:
THE FAT CAT ATE THE RAT
(this is how the code should read)
Here’s a handy table listing all the types of mutations:

46. Point mutation: a change in a single nucleotide
Example 1:
A SUBSTITUTION mutation
occurs where one nucleotide base is replaced by another.
example
THE FAT CAT ATE THE RAT
THE FAT HAT ATE THE RAT

47. Point mutations: types
Base (A,T,C,G) substitutions can lead to “Missense” or “Nonsense” mutations:
Missense: a change in DNA sequence that changes the codon to a different amino acid. This can alter the protein enough to render it nonfunctional.
Not all missense mutations are deleterious, some changes can have no effect.
Because of the ambiguity of missense mutations, it is often difficult to interpret the consequences.
Nonsense: a change in the genetic code that results in the coding for a stop codon rather than an amino acid.
The shortened protein is generally non-function or its function is impeded.

48. Point mutations can sometimes be “SILENT”.
How does this change the protein that this gene codes for?
More often than not, “third-base mutations” are silent. Why?
Another example:
Amino acid: leucine
GAA
GAG
GAT
GAC

49. Sickle-Cell Disease Affects one out of 400 African-Americans
Is caused by the substitution of a single amino acid in the hemoglobin protein in red blood cells
(shows seven out of the 146 amino acid units of normal hemoglobin)

50. Sickle Cell
Symptoms include physical weakness, pain, organ damage, and even paralysis
Sickle-cell disease occurs more commonly in people (or their descendants) from parts of the world such as sub-Saharan Africa, where malaria is or was common, but it also occurs in people of other ethnicities.
This is because those with one or two alleles of the sickle cell disease are resistant to malaria since the red blood cells are not conducive to the parasites.
In areas where malaria is common there is a survival value in carrying the sickle cell genes.

51. Sickle Cell Disease Genotypes:
Homozygous recessive individuals have sickle cell disease.
Heterozygous individuals are phenotypically normal, but exhibit a mild version of the disease; said to “carry” the trait for SC, but not actually have the disease (symptoms usually only altitude or heavy exercise).
Homozygous dominant individuals are phenotypically normal.
Genotypes:

52. Electrophoresis of the hemoglobin protein shows:
We see that homozygous normal people have one type of hemoglobin (A) and anemics have type S, which moves more slowly in the electric field. The heterozygotes have both types, A and S. In other words, there is codominance at the molecular level.
Try this pedigree of familial inheritance of SC disease

53. Point mutation: a change in a single nucleotide in a gene
Examples 2 & 3:
Insertion example
THE FAT CAT ATE THE RAT (original gene)
THE FAT CAT LAT ETH ERA T
Deletion example
THE FAT ATA TET HER AT
These substitutions are known as “Frameshift Mutations” because they shift the reading frame of the genetic message (triplets) so that the protein may not be able to perform its function.
Usually more serious than a substitution mutation. Why?

54. Follow this summary:

55. Remember: not all mutations are bad!
A harmful mutation is a mutation that decreases the fitness of the organism.
Sometimes, mutations can change a gene form in a nonharmful, or even beneficial, way.
“Polymorphisms”: slight variations in a gene that make us different, ex: eye colors, blood types, etc. Are these good or bad?
A mutation may enable the mutant organism to withstand particular environmental stresses better than non-mutant organisms, or reproduce more quickly. In these cases a mutation will tend to become more common in a population through natural selection. This is how populations EVOLVE over time.

56. Many mutations are neutral
A neutral mutation has no harmful or beneficial effect on the organism.
Many of these mutations occur in the noncoding DNA describes components of an organism's DNA sequences that do not encode for protein sequences.
More than 98% of the human genome does not encode protein sequences. We often call this “junk DNA” (extra).
Why are these “junk” sequences more likely to vary between individuals?

57. Chromosome Mutations
A chromosome mutation is an unpredictable (spontaneous) change that occurs in a chromosome.
These changes are most often brought on by problems that occur during meiosis (cell division that makes gametes) or by mutagens (chemicals, radiation, etc.).
Chromosome mutations can result in changes in the number of chromosomes in a cell or changes in the structure of a chromosome.
Usually MUCH more serious than a gene mutation. Why?

58. Changes in chromosome number or structureD E F G H
Deletion
Duplication M N O P Q R
Inversion
Reciprocal
translocation
A deletion removes a chromosomal segment.
A duplication repeats a segment.
An inversion reverses a segment within a chromosome.
A translocation moves a segment from one chromosome to another, nonhomologous one.
In a “reciprocal translocation", the most common type, nonhomologous chromosomes exchange fragments. 
What occurs in a “nonreciprocal translocation”?

59. Test your knowledge

60. Changes in Chromosomal Structure (animation)
The Consequence of Inversion (animation)

61. Recessively Inherited Autosomal Disorders
Many genetic disorders
Are inherited in a recessive manner (aa)
So, most affected individuals are homozygous (dual inheritance)
AA, Aa are normal phenotype, in this case
Recessively inherited disorders
Show up only in individuals homozygous for the allele
Carriers
Are heterozygous individuals who carry the recessive allele but are phenotypically normal

62. Cystic Fibrosis (recessive mutation in CFTR gene)
Symptoms of cystic fibrosis include
Mucus buildup in the some internal organs
Abnormal absorption of nutrients in the small intestine
Lung tissue from a cystic fibrosis patient, showing extensive destruction as a result of obstruction and infection.
H2O
Cl -
nebulizer
defective
channel
percussion
vest
thick mucus

63. Phenyketonuria
PKU is an autosomal recessive genetic disorder that is characterized by an inability of the body to utilize the essential amino acid, phenylalanine. Amino acids are the building blocks for body proteins.
In 'classic PKU', the enzyme (phenylalanine hydroxylase), that breaks down phenylalanine is completely or nearly completely deficient. (PAH gene, 12q23.2 )
This enzyme normally converts phenylalanine to another amino acid, tyrosine. Without this enzyme, phenylalanine and its' breakdown chemicals from other enzyme routes, accumulate in the blood and body tissues.
Infants are born “normal” but if not treated, severe brain problems, such as mental retardation and seizures, will occur.
Thus, this disease is GREATLY influenced by environmental factors: “multifactorial”

64. Other autosomal recessive disorders
Tay-Sachs disease
Albinism
Hemochromatosis types 1-3: the most common genetic disease in Europe.
You can watch this animation on inheritance of the HFE allele:

65. Dominantly Inherited Disorders
Some human disorders
Are due to dominant alleles One example is achondroplasia
A form of dwarfism that is lethal when homozygous for the dominant allele (DD)
Figure 14.15

66. Dominant allele Huntington’s disease
Is a degenerative disease of the nervous system
Has no obvious phenotypic effects until about 35 to 40 years of age
Lake Maracaibo, Venezuela
Village pedigree

67. X-linked disorders Sex-linked inheritance
More often found in males than females because recessive alleles are always expressed
Most X-linked disorders are recessive:
Color blindness: most often characterized by red-green color blindness
Duchenne’s muscular dystrophy (DMD): characterized by wasting of muscles and death by age 20
Fragile X syndrome: most common cause of inherited mental impairment
Hemophilia: characterized by the absence of particular clotting factors that causes blood to clot very slowly or not at all

68. X-linked disorders Sex-linked inheritance X B Y b Key
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. X B Y b
Key
=Unaffected female
=Carrier female
=Color-blind female
=Unaffected male
=Color-blind male
grandfather
daughter
grandson
X-linked Recessive
Disorders
• More males than females are affected.
• An affected son can have parents who have the normal
phenotype.
• For a female to have the characteristic, her father must
also have it. Her mother must have it or be a carrier.
• The characteristic often skips a generation from the
grandfather to the grandson.
• If a woman has the characteristic, all of her sons will
have it.

69. Mating of Close Relatives
Matings between relatives are called “consanguineous” matings
Can increase the probability of the appearance of a genetic disease (especially harmful recessive homozygotes)

70. X-linked disorders: Hemophilia
Sex-linked inheritance
X-linked disorders: Hemophilia
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Key
Unaffected male
Hemophiliac
Unaffected female
Carrier
Queen Victoria
Prince Albert
4 children of 9
are shown V
ictoria
Frederick III
(Germany)
Alice
Louis IV
(Hesse)
Princess
Helena of
Waldeck
Leopold
(died at 31)
Beatrice
Prince Henry of
Battenberg
12 children of 26
are shown
Henry
Irene
Frederick
(died at 3)
Alexandra
Nicholas II
(Russia)
Alice
Alexander
(Earl of
Athlone)
Alfonso XII
(Spain)
Victoria
Leopold
(died at 32)
6 children of 34
are shown
Waldemar
(died at 56)
Henry
(died at 4)
Alexei
(murdered)
Rupert
(died at 21)
Alfonso
(died at 31)
Gonzalo
(died at 20)
(queen): © Stapleton Collection/Corbis; (prince): © Huton Archive/Getty Images

71. Multifactorial Disorders
Many human diseases
Have both genetic and environment components
Examples include
Heart disease and cancer
Try this interactive family pedigree (nicotine addiction)

72. Genetic Testing and Counseling
Genetic counselors
Can provide information to prospective parents concerned about a family history for a specific disease

73. Counseling Based on Mendelian Genetics and Probability Rules
Using family histories
Genetic counselors help couples determine the odds that their children will have genetic disorders

74. Tests for Identifying Carriers
For a growing number of diseases
Tests are available that identify carriers and help define the odds more accurately
Fetal Testing
In amniocentesis
The liquid that bathes the fetus is removed and tested
In chorionic villus sampling (CVS)
A sample of the placenta is removed and tested

75. Prenatal Genetic Screening
Genetic Screening (karyotyping) is possible, prenatally
Chorionic villus sampling 9-14 weeks
weeks

76. Concept: Some inheritance patterns are exceptions to the standard chromosome theory
Epigenetics
Functional modifications to the genome that do not involve a change in the nucleotide sequence.
Environmental factors can alter the way our genes are expressed, making even identical twins different.
Examples of such modifications are DNA methylation and histone modification, both of which serve to regulate gene expression without altering the underlying DNA sequence.

77. Genomic Imprinting What Is Imprinting?
For most genes, we inherit two working copies -- one from mom and one from dad. But with imprinted genes, we inherit only one working copy. Depending on the gene, either the copy from mom or the copy from dad is epigenetically silenced. Silencing usually happens through the addition of methyl groups during egg or sperm formation. The epigenetic tags on imprinted genes usually stay put for the life of the organism. But they are reset during egg and sperm formation. Regardless of whether they came from mom or dad, certain genes are always silenced in the egg, and others are always silenced in the sperm.

78. (a) A wild-type mouse is homozygous for the normal igf2 allele.
Genomic imprinting
Involves the silencing of certain genes that are “stamped” with an imprint during gamete production
In mammals the phenotypic effects of certain genes depend on which allele is inherited from the mother and which is inherited from the father
(a) A wild-type mouse is homozygous for the normal igf2 allele.
Normal Igf2 allele
(expressed)
with imprint
(not expressed)
Paternal
chromosome
Maternal
Wild-type mouse
(normal size)
Mutant lgf2 allele
Dwarf mouse
Normal size mouse
When a normal Igf2 allele is inherited from the father, heterozygous mice grow to normal size But when a mutant allele is inherited from the father, heterozygous mice have the dwarf phenotype.

79. Genes located outside the nucleus also have influence
Extranuclear genes
Are genes found in organelles in the cytoplasm
The inheritance of traits controlled by genes present in the chloroplasts (ctDNA) or mitochondria (mtDNA)
Depends solely on the maternal parent because the zygote’s cytoplasm comes from the egg
Figure 15.18

80. In Humans:
Some diseases affecting the muscular and nervous systems are caused by defects in mitochondrial genes that prevent cells from making enough ATP
Examples of mitochondrial DNA diseases:
Leber's hereditary optic atrophy - causes progressive visual impairment
Kearns-Sayre disease
Progressive external ophthalmoplegia
Myoclonus epilepsy
MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes)
Mitomap - A human mitochondrial genome database