Genetics

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Questions Received:

  1. Does mutagenic always imply carcinogenic, and if so, why?

  2. What are homeobox genes? (Pre-Natal\Development)

  3. What has the means to make mutations?

  4. Who is the father of genetics?

  5. A brown-eyed man whose father was brown-eyed and whose mother was blue-eyed married a blue-eyed woman whose father and mother were both brown-eyed. The couple has a blue-eyed son. For which of the individuals mentioned can you be sure of the genotypes? What are their genotypes?

  6. Is the placenta genetic make up the same as the mother or the baby?

  7. What is the genotype of an individual with green eyes? Are they genotypically brown (BB or Bb) or are they genotypically blue (bb)?

  8. What are gene clusters?

  9. Having had positive DNA to identify my last partner as being my child’s father, he is stating that the colour of the child’s eyes can not make it possibly his. His eyes are a green hazel and mine are blue, yet my daughters are brown. He states this cannot be possible, is this right?

Responses:

What has the means to make mutations?

11th March 1999

Mutations are changes in the genetic information stored in cells. Various agents can cause mutations, for example radiation, viruses, and certain chemicals we come into contact with. But mutations are not just the result of damaging influences coming from outside the cells - some are the result of errors made within cells when they make copies of the genetic information before cell division. Most mutations are harmful, but some are not, and it is believed that they are the main source of genetic novelty and therefore central to the process of evolution. Some genes are more susceptible to mutation than others, and the view is forming that they provide something of a ‘toolbox’ for change. So mutations constitute a double-edged sword: causing problems for individual organisms but also driving evolution.

Genetic information is stored along molecules of DNA. The sequence of base-pairs along the DNA provides recipes for the 100,000 or so specific proteins that are needed by cells, and a mutation is a change to that sequence. Because DNA is vulnerable to damage, complex systems have been evolved within cells to check the integrity of the genetic information and repair it if necessary. This process of checking and repair is particularly important in cells which are dividing - forming copies of themselves. Normal cells will stop dividing if they detect an error that cannot be fixed, and may even close down completely (apoptosis). However, cancer cells disregard or bypass these normal control processes and continue dividing, creating the problems associated with tumour-development.

It is interesting that the need to eliminate harmful mutations has resulted in the evolution of sexual reproduction and mate choice. Most multicellular organisms are built up from diploid cells in which there are two similar sets of genetic information, one from the mother and the other from the father. This reduces the risk of a mutation creating problems - there is another potentially-normal version of the mutated gene for the cell to access. Failure to cope with harmful mutations has resulted in many small populations of organisms becoming extinct during evolution.

For an interesting review of mutations, see Brookes, M. (1998) Day of the mutators. New Scientist, 14 February, 38-42.

Who is the father of genetics?

12th April 1999

I am sure opinions will differ on this, depending on which country you live in and other factors, but I would suggest that Gregor Mendel is a possible candidate. Here are some notes about Mendel:

Gregor Mendel (4K bytes)Gregor Mendel: 1822-1884

At the age of 21 he became a member of the St Augustine Order (Roman Catholic). In later years he lived and worked in the Augustinian monastery in Brno, now part of the Czech Republic. From 1843 to 1868 he carried out experiments on garden peas and other plants in the garden shown below. He showed how characteristics are transmitted from one generation to the next. He determined that the height of the plant, the colour of the pea, and whether or not the peas had a smooth or wrinkled surface were controlled by what he called ‘unit characters' (later called genes by the dutch biologist Johannsen in 1909). His findings were published in 1866, but went unnoticed until about 60 years later.

 

< A picture of Mendel's garden

 

 

 

 

 

Mendel proposed 3 genetic laws:

A brown-eyed man whose father was brown-eyed and whose mother was blue-eyed married a blue-eyed woman whose father and mother were both brown-eyed. The couple has a blue-eyed son. For which of the individuals mentioned can you be sure of the genotypes? What are their genotypes?

12th April 1999

The best way to solve this type of genetic problem is to draw a pedigree. Before starting the pedigree, remember that we receive genes from both parents, and thus for a particular feature or trait that is governed by genes during development, there will be two versions of that gene in each cell. As to which gene of each pair is expressed - that will depend on the level of dominance of each gene. Some genes are more dominant than others, and will be expressed even if their partner is for a different trait. The gene for brown eyes is always dominant to the gene for blue eyes, so this means that for someone to be blue-eyed, they must receive a copy of the gene for blue eyes from their mother and another copy of the gene from their father. If they receive a gene for blue eyes from one parent and the other gene is for brown eyes, then they will develop brown eyes. Have a look at the pedigree below in which females are represented by circles and males by squares. The gene for brown eyes is called B, and the gene for blue eyes is labelled b. Work through the sequence given by the question, starting from the arrowed individual. You will see that all the genotypes can be worked out except for one - the father of the man in question:

Pedigree for eye colour

 

 

 

 

 

Is the placenta genetic make up the same as the mother or the baby?

16th April 1999

The placenta is a joint venture between tissues of the mother and baby, so the genes of both are present. The placental villi and the chorion from which they develop have the genetic makeup of the baby. The specialised endometrial tissues alongside have the genetic makeup of the mother. Given the genetic differences of the two tissues, it is surprising that the mother's immune system is not mobilised to produce a rejection reaction, as it would be if any other graft of genetically different cells was placed there. In some way, the baby's tissues are able to exist in close proximity with the maternal cells without that happening.

Diagrammatic section through the placenta(16K bytes)Diagrammatic section through the placenta: the maternal endometrial tissues are tinted purple, and the placenta tissues derived from the baby are tinted brown. The maternal blood circulating around the placental villi is shown in red.

 

 

 

 

 

What is the genotype of an individual with green eyes? Are they genotypically brown (BB or Bb) or are they genotypically blue (bb)?

23rd June 1999

The genotype of an individual with green eyes is bb which is essentially identical to that for blue eyes. However this does not explain the entire picture which involves the action of so-called modifier genes. Human eye colour is largely controlled by one gene with two alleles - a dominant allele, B for brown eyes and a recessive allele, b for blue eyes. Brown eyed people (BB or Bb) have branching pigment cells containing melanin in the front layer of the iris, whereas blue eyed people (bb) lack melanin in the front layer. This description of eye colour based on a single gene assumes therefore only two phenotypes: brown and blue. However we all know that eye colour comes in various shades: green, grey, hazel and black.

Probably no inherited characteristic is controlled exclusively by one gene pair. Even when only one principal gene is involved, its expression is influenced to some extent by other genes with individual effects which are so slight that they are difficult to locate and analyse. These are modifier genes and in the case of eye colour, these genes may affect the amount of pigment in the iris, the tone of the pigment (which may be light yellow, dark brown, etc) or its distribution over the surface of the iris. Green and grey eyes are genotypically bb; hazel and black eyes are BB. In rare cases, two blue-eyed people can have a brown-eyed child, because one of them, in whom the lack of pigmentation is a consequence of the action of modifier genes actually carries the genotype Bb instead of bb.

Reference

Keeton and Gould (1994) Biological Sciences (6th edition).

What are gene clusters?

18th March 2000

A gene cluster is a group of genes arranged close to each other on a chromosome and specifying proteins which contribute to a particular process or role. Here are two examples: the major histocompatability complex of genes that have a key role in the immune system, and the Hox clusters of genes which amongst other roles guide pattern formation in the early embryo.

Major Histocompatability Complex (MHC)

The MHC is a region on chromosome 6 containing 224 identified genes, of which 128 genes are probably expressed (The MHC sequencing consortium, 1999). This gene cluster was discovered over 50 years ago when systems of blood groups were being investigated, and during the last 30 years increasingly detailed gene maps have been built up. Approximately 40% of the expressed genes in this cluster contribute to the functioning of the immune system. Proteins coded by the type I and type II MHC genes function as receptors for peptides derived from the foreign proteins of pathogens such as bacteria or viruses, and the receptor/antigen complexes are presented to T cells (specialised white blood cells) which then prepare an appropriate immune response to eliminate the intruders. Since a huge range of non-self antigens is possible, a process of genetic recombination is required to ensure a sufficiently varied range of receptors, and this process of shuffling is facilitated by having the MHC genes arranged in close proximity to each other.

Hox Gene Clusters

Hox gene clusters are found in all animal genomes. They are a sub-group of the family of hundreds of homeobox genes which guide development. (For more information about homeobox genes, see our earlier answer.) In mammals there are 39 Hox genes arranged in 4 clusters on different chromosomes (Scott, 1999). Each gene contains as part of its sequence 180 base pairs (the "homeobox") that specify a DNA-binding region. This region enables the protein products of the Hox genes to be transcription factors which regulate the expression of other genes at critical stages in embryonic development. One of the key roles of Hox genes is the ordering of the embryonic axis into a cranio-caudal sequence of segments. One of the most striking and unexpected features of the Hox clusters is that the genes are arranged along the chromosome in the same pattern as the segments they control. It is believed that this colinear relationship may be important in ensuring correct gene regulation and consequent pattern formation.

References

Having had positive DNA to identify my last partner as being my child’s father, he is stating that the colour of the child’s eyes can not make it possibly his. His eyes are a green hazel and mine are blue, yet my daughters are brown. He states this cannot be possible, is this right?

10th December 2004

eye colour

For a long time, it was thought that eye colour was controlled by a gene that occurred in two forms, one capable of producing brown eyes, and the other producing blue eyes. In a situation like this, the two versions of the gene are referred to as alleles. The allele for brown eyes was considered to be dominant over the allele for blue eyes. This would mean that if at least one copy of the dominant gene was present, that would be enough for the baby’s eyes to be brown. Only if both the genes inherited by the baby were for blue eyes would the baby’s eyes be blue. Since according to this scheme we inherit one eye colour gene from our mother and the other from our father, different combinations of the two variants of the eye colour gene would occur each time a baby is conceived, depending on which allele is present in each gamete.

Therefore, according to this interpretation of eye colour, your last partner would be correct in saying that if you were both to have a child, the baby’s eyes could not be brown since neither of you - the parents - have brown eyes.

However, we now know that the genetic basis for eye colour is actually far more complex than this single gene-pair hypothesis suggests. Then, on top of this genetic complexity there are other factors that can influence eye colour, for example chemical factors such as prostaglandins. Also, in the last 18 months since publication of the human genome, attention has been shifting away from the 2% of the genome that consists of genes coding for proteins, towards the remaining 98% that is now thought to have other controlling effects during development. So it could be that the genes so far linked with eye colour are only a part of the explanation of how final eye colour is achieved.

Before looking at these influences on eye colour, it will be helpful to understand the physical basis of iris colour. Eye colour is determined mainly by the presence of a pigment called melanin. Brown eyes have a lot of melanin, while blue eyes have very little. Intermediate amounts of melanin produce eyes that are grey, green, hazel or different shades of brown.

The melanin is present in special cells called melanocytes in the iris of the eye. The number of melanocytes in the iris is relatively constant regardless of eye colour. There are two types of melanin in the iris melanocytes - eumelanin and pheomelanin. The ratio of eumelanin to pheomelanin will affect eye colour. The different shades of eye colour between dark brown and blue are believed to arise from shorter wavelengths of light being scattered from the fine meshwork of collagen within the iris. If the melanocytes of the iris contain a lot of pigment, most of the backscattered light is absorbed and the eyes will be brown, whereas if they contain only a little pigment then more backscattered light escapes and gives shades of green, grey, or blue.

By the mid-1990s, three gene pairs controlling human eye colour had been identified. Two of the gene pairs are present on chromosome pair 15 and one occurs on chromosome pair 19.

The bey 2 gene, on chromosome 15, has a brown and a blue allele. A second gene, located on chromosome 19 (the gey gene) has a blue and a green allele. A third gene, bey 1, located on chromosome 15, is a central brown eye colour gene.

Geneticists have designed a model using the bey 2 and gey gene pairs that explains the inheritance of blue, green and brown eyes. In this model the bey 2 gene has a brown and a blue allele. The brown allele is always dominant over the blue allele so even if a person is heterozygous (one brown and one blue allele) for the bey 2 gene on chromosome 15 the brown allele will be expressed. The gey gene also has two alleles, one green and one blue. The green allele is dominant to the blue allele on either chromosome but is recessive to the brown allele on chromosome 15. This means that there is a dominance order among the two gene pairs. If a person has a brown allele on chromosome 15 and all other alleles are blue or green the person will have brown eyes. If there is a green allele on chromosome 19 and the rest of the alleles are blue, eye colour will be green. Blue eyes will occur only if all four alleles are for blue eyes. This model explains the inheritance of blue, brown and green eyes but cannot account for grey, hazel or multiple shades of brown, blue, green and grey eyes. Also, it cannot explain how parents with green-hazel and blue eyes can produce a baby with brown eyes.

Eye colour genes, through the proteins they specify, influence the amount, type and placement of melanin in the iris. In general, Caucasian babies are born with bluish eyes because at the time of birth melanin has not yet been formed in their irises. Their eyes may then change to green, brown or other colours as melanin production begins. Babies of other ethnic origins such as African, Asian, Hispanic and Native American are often born with brown eyes because melanin production in the iris has started before birth. (Albinos have no pigment in their irises so the blood vessels in the back of the eye reflect light making the eyes look pink.)

The density of melanin granules appears to reach genetically determined levels by early childhood and usually remains constant throughout later life, although 10-15% of individuals exhibit changes in eye colour later in life. Some eyes become darker, but most become lighter with increasing age. These changes occur slowly over many years. The propensity to change eye colour may be an inherited trait like the eye colour itself.

Some medical treatments result in a change of eye colour. For example, increased iris pigmentation has been noted when prostaglandins are being administered to the surface of the eye (Stjernschantz et al, 2002). This change may be due to quantitative and qualitative alterations in the melanin content of the iris melanocytes. A darkening of eye colour has also been observed in youngsters experiencing surgery for cataracts.

A recent study of the genetics of eye colour has identified many more sites in the genome that have at least some influence on eye colour (Frudakis et al, 2003). Their approach was to look for tiny differences in the genome known as single nucleotide polymorphisms (abbreviated to SNPs) that are linked with eye colour. SNPs are DNA sequence variations that occur when a single nucleotide (A, T, C, or G) in the genome sequence is altered. Each individual has many single nucleotide polymorphisms that together create a unique DNA pattern for that person - these differences are often used as the basis for DNA ‘fingerprinting’. The analysis by Frudakis et al (2003) resulted in the identification of 61 SNPs linked with eye colour. The SNPs are located in 16 genes and other non-protein-coding regions of the genome. It was found to be impossible to link final eye colour with any single gene, suggesting that there is a complex interaction between all these genetic factors during development. Frudakis et al (2003) concluded that the previous results associating pigmentation gene alleles with iris colours are simply elements of a more complex picture of colour determination.

In conclusion, each one of us is a unique genetic experiment. Because of the way that the gametes (egg and sperm) are made, during which there is rearrangement of genetic material, and because of the element of chance involved in which sperm fertilises the egg, each new genome has unique characteristics. The more we learn about the factors determining eye colour, the more subtle and complex the process seems to be. So the earlier beliefs about the genetics of eye colour are being modified in the light of new evidence. Rather than a simple dominance of one allele over another, eye colour is now interpreted as an outcome of a developmental process involving many genetic interactions. In addition, eye colour can be modified by non-genetic factors such as prostaglandins. So although certain eye colours are more likely than others to occur in our children, given the eye colour of each parent, we cannot rule out the possibility of other, less likely, eye colours emerging in our children.

References

The following web site provides more information about human eye colour genetics and other human genetics topics:

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