1. Using Karyotypes To Diagnose Genetic Disorders
A regular human cell has 46 chromosomes: 44 autosomes, which come in pairs, and 2 sex chromosomes, which specify gender (XX for female and XY for male).
The pairs of autosomes are called "homologous chromosomes." One of each pair came from mom and the other came from dad. Homologous chromosomes have all of the same genes arranged in the same order, but with slight differences in the DNA sequences of the genes.
What happens when a person has something different, such as too many or too few chromosomes, missing pieces of chromosomes, or mixed up pieces of chromosomes?
                                                    
Using Karyotypes To Diagnose Genetic Disorders
A regular human cell has 46 chromosomes: 44 autosomes, which come in pairs, and 2 sex chromosomes, which specify gender (XX for female and XY for male).
The pairs of autosomes are called "homologous chromosomes." One of each pair came from mom and the other came from dad. Homologous chromosomes have all of the same genes arranged in the same order, but with slight differences in the DNA sequences of the genes.
What happens when a person has something different, such as too many or too few chromosomes, missing pieces of chromosomes, or mixed up pieces of chromosomes?
Using Karyotypes To Diagnose Genetic Disorders

3. So how are genes passed on from parent to child?
Chromosome
Gene
Genes - sections of chromosomal DNA
One set of chromosomes is inherited from each parent
Therefore, for each pair of genes, one is inherited from a person’s mother, and one from their father
Sometimes the genes, or chromosomes they are on, have defects which are passed to offspring
Homologous Chromosome pair
For example: ear lobe structure attached or unattached would be located on the same position on the same number chromosome from Mum and Dad

4. Classification of genetic disorders
Single Gene Disorders
Male
Mutations in single genes
Chromosome disorders
Whole chromosomes or sections messed up
Single Gene – Red represents altered gene in 1st top left pair of Chromosomes 1 altered and 1 unaltered – individual may or may not be affected by this (unless this is a dominant alteration)
2nd pair shows both genes altered – individual will be affected
3rd pair show the sex chromosomes with one alteration but as this is a male XY and the alteration is on the X the male will be affected as there is no counterbalance on the Y chromosome
Multifactoral – Genes rarely act alone e.g. Height they may have the gene for tall but if malnourished may be short. Changes in both genes can have different variants for example the gene for skin colour not just black and white but shades and environment Sun adding further colour or damage.
Chromosomal – Session 1 reminder extra chromosomes plus insertions and deletions
Chromosome number imbalance
Due to nondisjunction during meiosis
ex. Patau (Trisomy 13), Down syndrome (Trisomy 21)

5. Single gene disorders Caused by a mutant allele for a gene.
Mutant allele may be the dominant or recessive one
The three common types of single gene disorders are :
Autosomal recessive
Autosomal dominant
X-linked
AD – always expresses itself
AR - only expresses in the absence of dominant unaltered gene – healthy carrier
X – genes found on X chromosomes

6. Examples of Autosomal recessive diseases
Autosomal recessive inheritance
Must have Homozygous Recessive Genotype
Examples of Autosomal recessive diseases
Tay Sachs
Cystic fibrosis
Phenylketonuria (PKU)
Sickle Cell disease
Need both genes in an altered state to show the condition.
See NGEDC website ‘Search Conditions’ for further information on each of these conditions

7. Tay-Sachs
1 – 27 Ashkanazi Jews, Lousiana Cajuns and French Canadians – HIGHER FREQUENCY
in other population Heterozygotes have Selective Survival Advantage)
Problems with brain cell membrane chemical build up causes blindness and seizures and early death
Cystic fibrosis: the gene is GFTR based on chromosome 7q. It is a defective chloride ion transport in the cell membrane which leads to thickened mucus production outside the cell.
Fig. 1.2 ©Scion Publishing Ltd
Photos (a) and (b) courtesy of Dr Tim David

8. Cystic fibrosis Faulty cell membrane transport protein
Most common genetic disease among Caucasians
Faulty cell membrane transport protein
Cystic fibrosis: the gene is GFTR based on chromosome 7q. It is a defective chloride ion transport in the cell membrane which leads to thickened mucus production outside the cell.
Fig. 1.2 ©Scion Publishing Ltd
Photos (a) and (b) courtesy of Dr Tim David

9. Phenylketonuria “PKU”
Lacks enzyme to breakdown amino acid phenylalanine which builds up in brain
Cystic fibrosis: the gene is GFTR based on chromosome 7q. It is a defective chloride ion transport in the cell membrane which leads to thickened mucus production outside the cell.
Fig. 1.2 ©Scion Publishing Ltd
Photos (a) and (b) courtesy of Dr Tim David

10. Sickle cell disease
Sickle cell disease is an altered HBB gene on chromosome 11p. Abnormal haemoglobin is produced which results in sickle shaped red blood cells which can then lead to the blocking of small capillaries.
Ltd

11. AUTOSOMAL RECESSIVE INHERITANCE
Parents
Parent who are carriers for the same autosomal recessive condition have one copy of the usual form of the gene and one copy of an altered gene of the particular pair
The parents are usually healthy carriers
This is not unusual to be a carrier, so many individuals are unaware of their carrier status.
For example 1 in every 12 people in the UK are carriers for the cystic fibrosis gene.

12. AUTOSOMAL RECESSIVE INHERITANCE
Parents
Sperm/Eggs
A parent who is a carrier passes on either the usual gene
The other parent who is also a carrier for the same condition passes on either the usual gene or the altered gene into his/her eggs or sperm
or the altered gene into the eggs or sperm

13. AUTOSOMAL RECESSIVE INHERITANCE
Parents
Sperm/Eggs
Unaffected (carrier)
Unaffected (carrier)
Unaffected
The way to explain ‘chance’ this to the patient or parent is 1 in 4 or 25% chance of being affected or 75% chance of being unaffected 50% chance of being a carrier
Affected

14. D – No disease d- disease

15. Examples of Autosomal Dominant Disorders
Autosomal dominant inheritance
Homo dominant or Heterozygous
Examples of Autosomal Dominant Disorders
Achondroplasia (Dwarfism)
Huntington disease
See NGEDC website ‘Search Conditions’ for further information on each of these conditions

16. Achondroplasia Dwarfism

17. Huntingtons chorea

18. Autosomal dominant inheritance
Parents
Gametes
These slides show how and affected dominant gene is inherited by each conception. That this ‘chance’ occurs at each conception is a very important point as a miss-conception “ We have 1 affected child so the next one in a 50:50 chance will be unaffected” is a fairly common occurrence. The same probability is present for each child conceived and is not affected by previous pregnancies.

19. Autosomal dominant inheritance
Parents
Gametes At
conception
Ensuring that the students and therefore the parents understand ‘chance’ is key they need to use what is best for the patient
50:50 or 2 in 4 or 50%
Unaffected
Affected
Affected

20. Homozygotes must have two copies of the altered gene to be affected
Dominant
These individuals are called Heterozygotes with one copy of the altered gene they are affected
Recessive
Homozygotes must have two copies of the altered gene to be affected
Male
Hetero means ‘different’, homo means ‘same’
Homozygotes – received an affected chromosome from each parent who may have been healthy unaffected carriers
X-linked – always affected as they don’t have an X to balance the affected chromosome
X-linked recessive
Males with an altered gene on the X-chromosome are always affected

22. Examples of Autosomal recessive diseases
Autosomal recessive inheritance
Must have Homozygous Recessive Genotype
Examples of Autosomal recessive diseases
Tay Sachs
Cystic fibrosis
Phenylketonuria (PKU)
Sickle Cell disease
Need both genes in an altered state to show the condition.
See NGEDC website ‘Search Conditions’ for further information on each of these conditions

23. Examples of Autosomal Dominant Disorders
Autosomal dominant inheritance
Homo dominant or Heterozygous
Examples of Autosomal Dominant Disorders
Achondroplasia (Dwarfism)
Huntington disease
See NGEDC website ‘Search Conditions’ for further information on each of these conditions

24. Sex-Linked Traits Y
chromosome X
chromosome

26. What are Sex Linked Traits?
Most traits we inherit are located on our autosomes.
BUT
Some traits are determined by genes located on the sex chromosomes.
These traits are called sex linked traits

27. The X chromosome is larger in size and has many more genes than the Y chromosome. Those traits with genes on the X sex chromosome are called X-linked traits X
chromosome Y
chromosome

28. Gene Linkage
Sex-linked traits were discovered in 1910 by Thomas Hunt Morgan who studied inheritance in fruit flies (Drosophila).

29. Mendel’s Law of Independent Assortment applies to chromosomes which are assorted independently in meiosis.
Genes located close together are inherited together.

31. Sex linked Inheritance is different in males and females
Since males only have one X chromosome they can only receive one gene for these traits.
The gene is on the X chromosome they inherit from their mother
The Y chromosome, they got from their
father doesn’t have a copy of the gene

32. What he gets is what he is!!!
Males express all X-linked genes –
There’s no second allele to mask the effects of the only one he inherits on his X chromosomes

33. Males inherit one X chromosome
2 Possible Genotypes:
XᴿY or Xʳ Y

34. Females inherit two X chromosomes
3 Possible Genotypes:
XᴿXᴿ
XᴿXʳ
Xʳ Xʳ

35. Sex-Linked Traits – 1. Color Blindness – recessive disorder
2. Hemophilia – blood clotting disorder
3. Baldness – recessive trait
4. Muscular dystrophy – recessive disorder

36. Beyond Mendel’s Principle of Dominance
Incomplete Dominance
Codominance
Multiple Alleles
Polygenic Traits

37. Incomplete dominance
Dominant allele doesn’t fully mask the expression of recessive allele.
A “blending” of both dominant and recessive alleles is seen as an intermediate (inbetween) phenotype in heterozygotes.

44. Incomplete Dominance vs. Codominance
Incomplete dominance – Heterozygote’s traits are a blend of the two alleles
Ex. Red X White flowers > Pink flowers
Codominance – Both alleles for gene are equally strong and are both seen
Ex. Red x White feathers > Both colors seen

45. With incomplete dominance, a cross between organisms with two different phenotypes produces offspring with a third phenotype that is a blending of the parental traits.
With codominance, a cross between organisms with two different phenotypes produces offspring with a third phenotype in which both of the parental traits appear together.

46. Which inheritance pattern does each cross represent
Which inheritance pattern does each cross represent? Codominance or Incomplete Dominance X =
100% X =
100%
11/13/2018

47. IA IB i Multiple Alleles
Many genes come in more than just 2 forms – there can be many alleles for one gene
The gene for blood type comes in 3 different allele forms
IA IB i

49. Polygenic Traits More than one gene determines a trait
Usually the cause in traits with a lot of variation (height, skin color, hair color)

51. Phenotype results from the interaction of genes and environmental influences

52. Eye color is determined by many different genes
  Polygenic trait
2. Height and skin color comes in many forms on a continuum
  Polygenic trait
3. A hoo can have curly hair, spiked hair or a mix of curly and spiked
  Codominance – both traits seen
4. A horse has both red and white hairs making them look
pinkish (roan).
  Codominance – both traits seen
5. A puppy inherits a gray coat from its black coat dad and white mom Incomplete dominance – blended traits
 6. Snapdragons homozygous red crossed with pure white make pink Incomplete dominance – blended traits