LCSC06 directed study

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, so I suggest the relevant pages in Atkinson & McHanwell or alternatively Tortora et al as good sources Some of the slides have notes attached, so you might like to print off as ‘notes pages’ to assist you 2

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

Genotypes 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. 6 The expression of a genotype is termed a phenotype. For example, hair color, weight, or the presence or absence of a disease.

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

Bb BBBBb b bb Eggs Sperm 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). BB - Brown eyes Bb - Brown eyes bb - Blue eyes

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. Note that: the convention is that the dominant allele is denoted with a CAPITAL letter and the recessive allele a lower case 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).

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? 10

BB BBB B Eggs Sperm NB this gene is on an autosome not the sex chromosomes. A ‘Punnett’ diagram is used to work out the various combinations of gene alleles. So…..If both parents are homozygous brown eyed…… …the possible combinations are: So: all children will be brown eyed…….

Bb BBBBb BBBBb Eggs Sperm SO: all children still brown eyed but 50% chance homozygous and 50% heterozygous So another possible combination might be: if one parent is homozygous (BB) and the other heterozygous (Bb)

In the former case, the children who are heterozygous are carriers but do not display the phenotype of blue eyes themselves….remind yourself why this is the case…..? 13

Bb BBBBb b bb Eggs Sperm So : 25% chance of child being blue eyed 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….

NB: Brown / blue eye colour useful as a simple example, but in fact the genetics of eye colour is actually less straight forward.

Medical Genetics 16

Medical Genetics When studying genetic disorders, 6 general patterns of inheritance are observed: Autosomal recessive Autosomal dominant Autosomal C0-dominant X-linked recessive X-linked dominant Mitochondrial 17

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. Affected mothers and fathers 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.

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 19

20 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

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 GenotypePhenotype AAA AOA BBB BOB AB OOO

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.

XY XXXXY XXXXY Eggs Sperm Keep in mind: Boys gain their X chromosome from their mother – never their father. Girls gain one X chromosome from each parent.

XNXN Y0Y0 XNXN ♀NN♂ N- XnXn ♀Nn♂ n- Eggs Sperm 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). NB mutated genes are not always recessive or damaging

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…. An example of an X linked recessive trait is haemophilia

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X-linked dominant trait – e.g. fragile X syndrome 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 Fragile X syndrome, or Martin-Bell syndrome, is a genetic syndrome which results in a spectrum of characteristic physical, intellectual, emotional and behavioural 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.

Mitochondrial inheritance e.g. Leber's hereditary optic neuropathy (LHON) 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. 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…because…? 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.

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