1. Basic Concepts in Human GENETICS
Pedro Amarante Andrade, PhD
LCSC06 BIOSCIENCES FOR SPEECH AND LANGUAGE THERAPY

2. READ THROUGH THE FOLLOWING SLIDES
You may find that you need more of an introduction to the topic if this aspect of bioscience is totally new to you. Therefore, you should read the chapters on genetics in Atkinson & McHanwell or Tortora
Some of the slides have notes attached, so you might like to print off as ‘notes pages’ to assist you

3. CHROMOSOME Made of DNA, protein, and RNA;
Single piece of coiled DNA – contains genes, regulatory elements and other nucleotide sequences
Encodes most of all of the organism’s genetic information
A chromosome is a structure made of DNA, protein, and RNA found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control
its functions. Chromosomal DNA encodes most or all of an organism's genetic information.

4. CHROMOSOME Are found in the nucleus of cells,
All but the gametes contain 23 pairs (22 pairs of autosomes and one pair of sex chromosomes)
One chromosome in each pair comes from each parent
The two chromosomes in a pair are typically homologous i.e. contain the same genes, which control the same traits
Two alternative forms of the same gene are called ALLELES
One may be normal and the other abnormal
One may be dominant, the other recessive

5. CHROMOSOMAL ABNORMALITIES
23 pairs of chromosomes
50+ different chromosomal abnormalities
Too many chromosomes
Too few chromosomes
Vast majority of chromosomal abnormalities are lethal (spontaneous abortion)
Discuss Turner’s syndrome XO and Klinefelters XXY syndrome briefly

6. HUMAN KARYOTYPE Most human cells contain 46 chromosomes:
22 pairs of chromosomes named autosomes
2 sex chromosomes (X,Y):
XY – in males
XX – in females

7. GENOTYPES vs PHENOTYPES
In autosomes chromosomes exists in homologous pairs
At each locus (except for sex chromosomes) there are 2 gene alleles. One allele at an individual locus on each of the pair of chromosomes. This constitutes the individual’s genotype at that locus and for that individual gene.
The expression of a genotype is termed a phenotype. For example, hair color, weight, or the presence or absence of a disease

8. HAPLOID AND DIPLOID CELLS
Remember that body (somatic) cells have chromosomes arranged in pairs (diploid), whilst gametes (sperm and ova) have only one member of each pair (haploid)
Diploid cells will therefore have gene alleles arranged in pairs*, whilst the gametes will have only a single gene allele
*except in males where the Y chromosome is shorter than the X

9. DOMINANT AND RECESSIVE ALLELES
Many genes exist in two allelic forms in which one allele is dominant to the other which is termed recessive
For example in human eye colour – brown eyes (B) is dominant to blue (b).
SPERM B b BB Bb bb
EGGS
BB - Brown eyes
Bb - Brown eyes
bb - Blue eyes

10. DOMINANT AND RECESSIVE ALLELES
In diploid somatic cells the genotype with respect to an individual gene (e.g. the gene for eye colour) can be described as homozygous if both alleles for the gene are the same – so could be homozygous dominant (BB) brown or homozygous recessive (bb) blue.
SPERM B b BB Bb bb
EGGS
BB - Brown eyes
Bb - Brown eyes
bb - Blue eyes

11. DOMINANT AND RECESSIVE ALLELES
Note: the convention is that:
DOMINANT allele (CAPITAL letter)
recessive allele (lower letter)
If the alleles are different (Bb) the condition is called heterozygous and in this example the individual would be brown eyed because brown (B) is dominant to blue (b).
SPERM B b BB Bb bb
EGGS
BB - Brown eyes
Bb - Brown eyes
bb - Blue eyes

12. TRY THIS EXAMPLE
Two brown eyed parents have three children – two brown eyed and the other blue.
Q. What must the genotypes of the parents be?

13. All children will be brown eyed
THE ‘PUNNETT’ DIAGRAM
A ‘Punnett’ diagram is used to work out the various combinations of gene alleles
E.G. If both parents are homozygous brown eyed the possible combinations are:
SPERM B b BB
EGGS
All children will be brown eyed

14. THE ‘PUNNETT’ DIAGRAM Another possible combination might be:
if one parent is homozygous (BB) and the other heterozygous (Bb)
the heterozygous children are carriers but do not display the phenotype of blue eyes themselves
SPERM B b BB Bb
EGGS
All children still brown eyed but 50% chance homozygous and heterozygous

15. 25% chance of a blue eyed child
THE ‘PUNNETT’ DIAGRAM
The final possibility is if both parents are heterozygous (Bb)
..this results in the possibility of having both blue eyed as well as brown eyed children….
SPERM B b BB Bb bb
EGGS
NB: Brown / blue eye colour useful as a simple example, but in fact the genetics of eye colour is actually less straight forward.
25% chance of a blue eyed child

16. MEDICAL GENETICS

17. MEDICAL GENETICS
When studying genetic disorders, 6 general patterns of inheritance are observed:
Autosomal recessive
Autosomal dominant
Autosomal Co-dominant
X-linked recessive
X-linked dominant
Mitochondrial

18. MEDICAL GENETICS Autosomal Recessive
Recessive inheritance means both genes in a pair must be defective to exhibit the defect
The disease appears in male and female children of unaffected parents
e.g. cystic fibrosis
Cystic fibrosis (also known as CF) is a genetic disorder known to be an inherited disease of the secretory glands, including the glands that make mucus and sweat. The major organ systems affected are the respiratory system and the gastrointestinal tract.

19. MEDICAL GENETICS Autosomal dominant
The disorder appears when only one of the two genes of a chromosome pair is defective
Affected males and females appear in each generation of the pedigree
Dominant genes for severe disorders are usually lethal: result in death of embryo/foetus.
An exception: Huntington's disease [or chorea or 'disorder‘] (HD) is an incurable neurodegenerative genetic disorder that affects muscle coordination and some cognitive functions, typically becoming noticeable in middle age. It is the most common genetic cause of abnormal involuntary writhing movements called chorea.

20. MEDICAL GENETICS Autosomal dominant
Mothers or fathers can transmit the phenotype to both sons and daughters
The risk of a mutation carrier transferring disease to offspring amounts to 50%.
e.g. Huntington’s disease
Dominant genes for severe disorders are usually lethal: result in death of embryo/foetus.
An exception: Huntington's disease [or chorea or 'disorder‘] (HD) is an incurable neurodegenerative genetic disorder that affects muscle coordination and some cognitive functions, typically becoming noticeable in middle age. It is the most common genetic cause of abnormal involuntary writhing movements called chorea.

21. MEDICAL GENETICS FOXP2 gene
FOXP2 is a protein that in humans is encoded by the FOXP2 gene, which is located on human chromosome 7. In humans, mutations of FOXP2 cause a severe speech and language disorder. The gene is transmitted in an autosomal dominant pattern. The following article provides some background to the gene and its expression in humans.
Read more about FOXP-2 and link to SLI in Cummings, L p284

22. CO-DOMINANT OR MULTIPLE ALLELE INHERITANCE
(ABO BLOOD GROUPS)
The gene has three allelic forms A and B are co-dominant and O is recessive
Genotype
Phenotype AA A AO BB B BO AB OO O

23. GENES PRESENT ON THE SEX CHROMOSOMES
The X chromosome is larger than the Y chromosome and has a segment for which there is no equivalent on the Y chromosome. This segment contains genes where the alleles are not matched by alleles on the Y chromosome. In males the single allele on the X chromosome will always show itself in the character (phenotype) of the individual. In females with two X chromosomes a recessive allele may be masked by a dominant allele on the other X chromosome.

24. GENES PRESENT ON THE SEX CHROMOSOMES
Boys gain their X chromosome from their mother – never their father. Girls gain one X chromosome from each parent.
SPERM X Y XX XY
EGGS

25. * mutated genes are not always recessive or damaging
GENES PRESENT ON THE
SEX CHROMOSOMES
When considering sex linked traits we must take account of the chromosome type (X or Y) as well as the allele present (or not present) on each.
For example consider a gene on the X chromosome, which has a ‘Normal’ dominant form (N) and a mutant* recessive form (n)
* mutated genes are not always recessive or damaging
SPERM XN Y0
♀NN
♂ N- Xn
♀Nn
♂ n-
EGGS

26. (Remind yourself why this must be so)
GENES PRESENT ON THE
SEX CHROMOSOMES
X linked recessive traits
Many more males than females show the condition
All the daughters of an affected male will carry the condition and are ‘carriers’.
None of the sons of an affected male show the condition or are carriers.
(Remind yourself why this must be so)
E.g. haemophilia
SPERM XN Y0
♀NN
♂ N- Xn
♀Nn
♂ n-
EGGS

27. GENES PRESENT ON THE SEX CHROMOSOMES X linked recessive traits
None of the sons affected: daughters are carriers. What happens if one of these carrier daughters mates with an unaffected man?
X linked recessive, carrier mother: There is a chance that a son can be affected. Haemophilia is passed down the generations in this way – for example, see Queen Victoria’s family tree.

28. GENES PRESENT ON THE
SEX CHROMOSOMES
X linked recessive traits

29. GENES PRESENT ON THE SEX CHROMOSOMES X-linked DOMINANT trait
Affected males pass the disorder to all daughters but to none of their sons
Affected heterozygous females and unaffected males pass the condition to half their sons and daughters
e.g. fragile X syndrome

30. GENES PRESENT ON THE SEX CHROMOSOMES
X-linked DOMINANT trait - e.g. fragile X syndrome
Fragile X syndrome, or Martin-Bell syndrome, is a genetic syndrome which results in a spectrum of characteristic physical, intellectual, emotional and behavioral features which range from severe to mild in manifestation. The syndrome results in a failure to express a protein which is required for normal neural development.

31. GENES PRESENT ON THE
SEX CHROMOSOMES
X linked dominant traits

32. e.g. Leber's hereditary optic neuropathy (LHON)
MEDICAL GENETICS Mitochondrial inheritance
In sexually reproducing organisms, mitochondria are normally inherited exclusively from the mother. The mitochondria in mammalian sperm are usually destroyed by the egg cell after fertilization.
e.g. Leber's hereditary optic neuropathy (LHON)

33. MEDICAL GENETICS Mitochondrial inheritance
Mitochondrial disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass mitochondrial traits to their children

34. MEDICAL GENETICS Mitochondrial inheritance
Leber’s hereditary optic neuropathy (LHON) or Leber optic atrophy is a mitochondrially inherited (mother to all offspring) degeneration of retinal ganglion cells (RGCs) and their axons that leads to an acute or sub acute loss of central vision.

35. CHECK YOUR UNDERSTANDING
What is the meaning of (i.e. in relation to genetic concepts):
Chromosomes
Autosomes
Alleles (homozygous and heterozygous
X-linked
Y-linked
Dominant
Recessive