Genetics Flashcards
What do genetic diseases affect?
They affect genes individually or entire chromosomes. Although these are rare diseases, they represent a significant clinical load.
How common are single gene disorders?
These are individually rare (the most common affection ~1/500 people), but together are estimated to affect ~1.5 % of the population. There are currently over 5500 single gene diseases described. These single gene disorders affect all body systems and hence all specialties and result in a large health burden.
How common are chromosomal abnormalities?
These are estimated to affect 1/150 live births (1-2% of the population). They occur when chromosomes are damaged during formation, either in the sleek or egg, or during early formation of the embryo.
Outline genetic inheritance
Human genetic material is encoded in chromosomes, of which there are 25000 genes. There are 46 chromosomes (23 pairs) and 22 autosomal pairs. The sex chromosomes (XX or XY) are the only non-autosomal pair. DNA is obtained from the father and mother.
Outline mitochondrial DNA
Mitochondrial DNA (mtDNA) in humans is around 16500 base pairs and encodes 15 proteins, rRNA and some tRNAs. All mitochondrial DNA is derived from the mother. Most mitochondrial proteins are encoded by the cell genome and only a minority encoded in the mitochondria themselves.
What is a gene?
They can exist in a variety of forms, in each form of the gene is called an allele:
1) Homozygous: Someone with two identical alleles of a gene
2) Heterozygous: someone with two different alleles of a gene
3) Locus: position of the gene on a chromosome
Outline human genetic disorders
Sometimes a gene is mutated or missing, which can lead to disease. Everyone has several deleterious mutations.
What are complex disorders?
These are common diseases that result from a combination of genetic and environmental factors interacting (e.g. obesity and type II diabetes).
What is autosomal dominance?
A characteristic is dominant if it manifests in a heterozygous (ie two different alleles at a locus). Dominance refers to the phenotype, not the genotype.
What are dominant autosomal disorders?
They are a single gene/allele disease or trait. The disease is passed down to offspring with multiple generations affected. Each affected person normally has one affected parent. Each child of an affected person has a 50% change of being affected. Makes and females are equally likely to pass on these conditions, allowing a vertical pedigree pattern.
What makes a genetic mutation dominant?
Tend to be either:
1) Gain of function - gene now makes a protein with a new function to the original (e.g. longer lifespan/new location), thus increasing their effect
2) Dominant negative effect - the mutated form interferes with the activity of proteins it binds (e.g. dimer or multiverses), which reduces activity
3) Insufficient protein (rare) - mutation in one gene results in half the amount of a protein needed for normal function
What are carriers of autosomal recessive disorders?
Carriers have lost a single copy of a gene but the normal one is sufficient to maintain normal function.
What are autosomal recessive disorders?
Recessive means that two copies of the abnormal (non-working) gene must be present in order for the disease or trait to develop. These tend to be ‘loss of function’ mutations (e.g. deletions). Parent and children of affected people are normally unaffected. One of more siblings is affected. Each subsequent sibling of an affected child has a 25% change of being affected, with makes and females equally affected. This allows a horizontal pedigree pattern.
Outline the link between consanguineous (incestuous) marriages and autosomal recessive disorders
20% of the world’s population live in areas with preference for consanguineous marriages. These marriages elevate the risk of autosomal recessive diseases and rarer diseases. If the family (e.g. the Hapsburg family) has multiple consanguineous marriages, the affected individuals may be seen in several generations.
Outline the sex chromosomes
1) The X chromosome: consists of 1000-1300 genes, with ~850 of these genes being protein coding.
2) The Y chromosome: much smaller than the X chromosome and consists of only 150 genes, with 50-70 of these genes being protein coding.
Outline recessive X-linked disorders
They affect mainly males- effectively acting as dominant. Females can be carriers and affected makes are linked through females. Affected boys may have affected uncles on their mother’s side. Females who are homozygous for the mutation also have the disorder. Parents and children of affected people are most commonly unaffected.
How are recessive X-linked disorders inherited?
Brothers of an affected son have a 50% risk of having the disorder. Sisters have a 50% change of being a carouse. All daughters of a man with an X-linked disorder, will be carriers, as men only have one X chromosome. All sons of this father will be healthy as they would have only inherited the Y chromosome from their father.
Outline dominant X-linked disorders
These are similar to the autosomal dominant pattern, as it is seen in both sexes. All daughters but no sons of an affected father are affected, whereas both sons and daughters of an affected mother can be affected. The condition is often milder and more variable in females than in males, due to random X inactivation in some tissues. Some diseases are only evident in females, as males are not viable, due to their only having one X chromosome.
Outline Y linked disorders
These only affect males and affects all the sons of an affected male. These show a vertical pedigree pattern.
What are mitochondria?
These are specialised organelle of eukaryotic cells that share an evolutionary past with bacteria - endosymbiosis, and have their own DNA. The majority of mitochondrial proteins are encoded by nuclear genes, but mutations in these genes cause most mitochondrial diseases. Some mitochondrial diseases are caused by mutations in mitochondrial DNA.
Outline mitochondrial inherited disorders
These are diseases caused by mutations in mitochondrial DNA. All mitochondria and maternally (from the mother) inherited. This means that all children of an affected woman may be affected. Children of affected men are never affected. This shows a vertical pedigree pattern, however mitochondrial diseases are typically extremely valuable, even within a family.
Outline the two factors that play a role in mitochondrial variability
1) Heteroplasmy: mitochondria have multiple copies of their genome, with some being normal some being mutant. They only express effects of a disease above a threshold number of mutant genomes. Mitochondria endosymbiosis (bacterial origin) means that they can replicate by binary fission, allowing them to lose or gain mutated genes.
2) Number of affected mitochondria within cells: mitochondria segregate randomly during cell division. The disease will only develop once the threshold has been reached for the number of mutant mitochondria in each cell. The number of mutant mitochondria can change with time. Many of these diseases develop with age, due to and accumulation of mutant mitochondria.
What is collagen?
Collagen is an extracellular matrix protein synthesised by and secreted from a variety of cells, such as fibroblasts, and organised into insoluble fibres.
What is the function of collagen fibres?
Collagen fibres are a major part of the extracellular matrix surrounding cells and giving mechanical strength and rigidity to tissues and organs. In particular they provide the tensile strength of skeletal tissues including bone, cartilage, tendons and ligaments.
How many major types of collagen are there?
There are at least five major types of collagen which occur in different tissues.
Outline the structure of collagen
Each type of collagen has distinct properties, but they all have the same triple helix structure which is the special feature of collagen. Associated with this is the unusual amino acid composition with its high concentration of glycine. Glycine is the smallest of the amino acids and occurs at every third position in collagen where it faces the interior of the helix (Gly-x-y repeated). Other features are the presence of the modified amino acids hydroxyproline and hydroxylysine.
What are the main features of osteogenesis imperfecta (OI)?
The main feature of this disease is repeated fracture of long bones, and for this reason it can easily be misdiagnosed as child abuse. There are also malformed bones. There is a whole range of genetic disorders which can lead to the disease.
What causes most cases of OI?
Most cases of osteogenesis imperfecta result from mutations in the glycine residues producing defective structural assembly.
What effect would a mutation in OI have on the protein sequence?
This substitution of the normal glycine at this residue, with a larger amino acid, in the mutant molecule, will cause steric hindrance which generates a kink in the normally straight triple helix, with a resulting defect in the assembly into fibres.
When might a change cause an altered electrophoresis pattern?
If the amino acid introduced is cysteine, inappropriate disulphide bonds would form between the two α1(I) chains in the helix, due to a reactive sulphydryl group in the cysteine side chain. Thus not only is formation of the collagen triple helix disrupted, but the resulting crosslinked polypeptide chains will migrate much more slowly than the individual chains when examined by gel electrophoresis in the presence of SDS.
What is the role of 2-mercaptoethanol in electrophoresis?
The disulphides bonds will be cleaved in the presence of
2-mercaptoethanol, allowing the chains to migrate according to their molecular weight.
Why are only some of the α1(I) collagen chains affected in people heterogenous for OI?
Due to the patient being heterozygous, only some of their α1(I) chains will be abnormal while the other allele makes the normal α1(I) chains. In principle 50% of the chains would be normal and 50% abnormal, though in practice this exact ratio rarely occurs in real genetic diseases.
Why does the exact 1:1 abnormal to normal chains rarely occur in practice in real genetic diseases?
There may be differences in the rates of transcription of the gene, rate of translation, stability of mRNA or stability of the protein which lead to a different ratio.
Why is the OI gene dominant?
Because the collagen triple helix contains two α1(I) chains and will be disrupted if only one is the mutant form, the majority of the collagen fibres will be affected leading to a dominant phenotype.
What is the major consequence of OI?
The major consequence is in the formation of bone. Bone is formed by laying down hydroxyapatite (a form of calcium phosphate) on an ordered scaffold of collagen-I. The abnormal collagen structure leads to defects in this mineralisation process, so that the patient ends up with skeletal abnormalities and generally weak bones.
Why is testing for OI different in prenatal diagnosis?
Most patients suspected of having OI are investigated by direct study of their collagen protein. This would not be a suitable approach for prenatal diagnosis since sampling of collagen from a fetus would be impractical and risky (could lead to miscarriage).
Outline genetic screening of prenatal DNA for OI, using PCR
The foetal DNA is obtained by chorionic villus sampling or amniocentesis and amplified by PCR. Specific probes could be used which were complementary to part of the DNA sequence where a mutation was known to occur: under the right conditions of temperature and ionic strength, the probe will only hybridise (bind to the DNA) if it has the exact complementary sequence, enabling normal and mutant genes to be distinguished.
Outline genetic screening of prenatal DNA for OI, using restriction enzymes
If the mutation altered a restriction enzyme recognition site, that would allow identification of normal and mutated DNA since only one would be cleaved by the enzyme to shorter fragments.
How are people represented in a pedigree diagram?
1) Unaffected male = white square
2) Unaffected female =white circle
3) Affected male = black square
4) Affected female = black circle
5) Autosomal carrier male = half black-half white (vertically) square
6) Autosomal carrier female = white circle
7) X-linked carrier female = white circle with a central black dot
8) Deceased male = white square with a horizontal line across
9) Deceased female = white circle with a horizontal line across
10) Proband (seeking medical attention) male = white square with a small arrow on the bottom left pointing to the opposite corner
11) Proband (seeming medical attention) female = white circle with a small arrow on the bottom left pointing diagonally
How are relationships depicted in a pedigree diagram
1) Couple = mates linked by a horizontal line
2) Consanguineous couple = linked by two horizontal lines
3) Offspring = linked to parents by horizontal line
4) Dizygotic (non-identical) twins = linked to each other by diagonal lines
5) Monozygotic (identical) twins = linked to each other by diagonal lines, and a horizontal line joining the two diagonal lines
6) Generations = each one is on a separate line and denoted with Roman numerals (e.g. I = grandparents, II = parents, III = offspring)
7) Offspring = birth order general left to right, children can also be numbered left to right
8) Lineage = maternal on the left, paternal on the right
What is the purpose of a pedigree diagram?
1) Provides a clear simple summary of information
2) Allows patterns to be spotted easily
3) Allows patterns to be explained to patients
4) Allows identification of potential carriers of risk gene
5) Allows the risk of passing on disease or being a carrier to be calculated
6) Permits informed choice, as many diseases are a mix of familial and sporadic (e.g. motor neurone is ~85% sporadic and ~15% familial - four known genes account for 65% of cases)
How are pedigree diagrams drawn?
1) Drawn from the bottom, starting with the proband and siblings
2) One parent is chosen at a time, with their siblings, children and parents drawn
3) The other parent’s side of the family is then added
4) Children of other partners are then added
What are the potential difficulties of drawing a pedigree diagram
1) Incomplete information
2) May not have information on all or many relatives
3) Incorrect information
4) Family history may not be correct
5) Important in clinical setting
Outline autosomal dominant inheritance in a pedigree diagram
1) Vertical transmission
2) Not all offspring affected
3) Males and females affected (50% risk of inheritance)
4) At least one affected parent (mother or father)
Outline X-linked recessive inheritance in a pedigree diagram
1) Not all generations affected (affected fathers do not have affected offspring unless partner is affected/carrier)
2) Not all offspring affected (mutated gene has no effect on own, but some female offspring will be carriers)
2) Only Males affected (gain X chromosome from their mother)
2) Inherited from unaffected mother (carrier but unaffected)
Outline mitochondrial inheritance pedigree diagrams
1) Vertical transmission
2) All generations affected
3) All offspring affected (mutation inherited from affected mother)
4) Males and females affected (100% risk of inheritance)
What is the role of mitochondria in inheritance?
Mitochondria have multiple copies genome some normal some mutant. Offspring inherit different numbers of mutated mitochondria from mother. Different tissues/cells can contain different number of mutated mitochondria and this can change with time. Some diseases develop with age due to accumulation of mutated mitochondria. all mitochondrial disease caused by mutations in mitochondrial DNA, most are caused by mutations in cell genome and have normal mendalian inheritance.
Outline autosomal recessive inheritance in pedigree diagrams
1) Usually no family history of disease
2) Parents unaffected (mutated gene has no effect on own)
3) Horizontal transmission –siblings, cousins affected
4) Not all offspring affected (require 2 mutated copies to express disease)
5) Males and females affected
6) Possibly consanguinity (incest) in pedigree
7) Obligate carriers
What is risk in pedigree diagrams?
This is a calculation of the predicated chance of having the disease or being carrier. It is calculated by working from person with known phenotype to subject (closest relative on each side of family) and multiplying the risks together.
What must be taken into account when calculating risk in pedigree diagrams?
All information must be taken into account, including:
• Phenotype
• Disease characteristics
• Family distribution for X-linked and mitochondrial disease
• Which side of family disease is on
• Which parent has the disease
What are risk modifiers in pedigree diagrams?
• Which side of family disease is on > X-linked, mitochondrial • Ethnic background > Many diseases have different prevalence in different populations (e.g. CF, Sickle cell, Tay-Sachs) > Heterozygote advantage (e.g. sickle cell, CF) >Founder effect (e.g. Tay-Sachs) • Information about the patient > Their phenotype > Their biological sex
How is Osteogenesis imperfecta classified?
It is now classified into nine subtypes, which although they all result in fragile bones prone to fracture they have different disease outcomes, inheritance patterns and underlying causes (those caused by mutations in collagen genes and those caused by mutations in other genes).
Outline the role of gene/environment interaction
Even though the underlying cause of these diseases are genetic there is an important role for the environment in the progress and outcome of the disease for each patient. Here, environment means factors external to the patient.
How does environment affect Multiple Endocrine Neoplasia type 1 (MEN1)?
The condition is inherited in an autosomally dominant fashion, but despite this not all people with the mutation will develop the same types of adenoma or at the same time. This is because a second event has to occur to promote tumour formation. Some people develop many tumours at a young age whereas others do not develop any tumours until very late in life. The exact cause of this is unknow but there is clearly an effect of environmental impact on the course of the disease.
How spokes sex effect disease?
There are a number of physiological differences between males and females and these differences can affect the phenotype dispalyed by individuals harbouring the same mutations. At the most simple level this can be due to the presence or absence of organs and tissues. So for example men with mutations in BRCA-1 and BRCA-2 have an increased risk of prostate cancer. This is obviously not the case with females as they lack a prostate instead they have an icreased risk of ovarian cancer.
Why does a Hereditary Hameochromatosis develop differently in men and women?
In men the symptoms begin to develop between 40 and 60 whilst in women symptoms do not develop until several years after menopause. The explanation for this is that females lose a significant amount of blood during menstruation and this prevents the build up of iron in other tissues. Men also tend to have more severe phenotypes. This though is not absolute as some men do not develop symptoms whilst some women do.
How does the presence of other genes effect disease?
In addition to the presence of the disease gene the life course of a disease and the symptoms presnt are commonly modified by the presence of other genes. These genes can either improve the condition or make the condition worse.
How does the presence of multiple genes affect eye colour?
The type of OCA-2 inherited is resonsible for approximatley 80% of eye colour. The rest is controllled by other genes. The second most important gene is one called HERC2, which controls the activity of OCA- In addition to HERC2 there are over 16 other genes that influence eye colour. The interaction of which produce a wide range on eye colours
How can the same gene have a different mutation and phenotype?
Some diseases are associated with only a single mutation for example sickle cell anemia. Where as other disease can arise as the result of many mutations within the same gene. Both Duchenne and Becker muscular dystrophy are caused by mutations in the dystrophin gene; the largest known human gene. the diseases are similar in the distribution of muscle wasting and weakness, which is mainly proximal. The reason for these diffences in disease progression are the type of mutation in each. Both are the result of deletions in the dystrophin gene but in In DMD the mutation is a frame shift deletion, but in Becker Muscular dystophy the mutation does not result in a frame shift.
What are trinuecleotide repeat disorders?
These are a large group of diseases caused by a trinucleotide repeat expansion. This is a mutation in which a region of three repeated nucleotides in the genome increases in number during DNA replication. If there are fewer than 27 repeats in the genome, these tend to be stable and the function of the protein remains normal. As the number of repeats increases, it reaches a thresehold above which they are no longer stable during DNA replication and the number of repeats increases during subsequent rounds of DNA replication. This increase in trinucleotide repeats changes the protein function and a greater number of repeats results in a more severe phenotype.
How does trinucloetide repeat cause Huntingdon’s disease?
Huntington’s disease is caused by expansion of a region of cytosine-adenine-guanine (CAG)—repeats, in the huntington gene. CAG is the codon for glutamine, so a series of these repeats results in the production of a chain of glutamine known as a polyglutamine tract or Poly Q tract (Q being the single letter code for glutamine).
1) < 27 repeats: normal phenotype and the region is stable.
2) 27–35 repeats: an Intermediate phenotype with some minor effects, however the region of the DNA is not longer stable and the numbers of repeats can increase.
3) 36–39 repeats: results in the characteristic phenotype but not all carriers will be affected by the disease.
4) 40 or more repeats: results in Huntington’s disease in all carriers.
Define karyotype
This is mainly a collection of a person’s chromosomes, which is most easily determined using a sample of peripheral blood, but can also be determined in amniotic cells and chronic villus sample.
How are karyotypes prepared?
1) Collect ~5ml heparinised venous blood
> Can use amniotic cells, CVS
2) Isolate white cells
3) Culture in presence of phytohaemagglutinin
>Stimulates T-lymphocyte growth/differentiation
4) After 48 hours add colchicine
> Causes mitotic arrest – metaphase
5) Place in hypotonic saline
6) Place on slide
7) Fix and stain
What is a karyotype gisema stain?
Once the stained sample has been obtained, individual chromosomes are cut out and arranged. Karyotype is now often done in prophase rather than metaphase, as the chromosomes are less compact, allowing more detail from the karyotype.
Outline DNA compaction
DNA does not exist as a single double helix, but is compacted around his tones and further condensed into chromatin. The function of chromatin is not only fitting a lot of DNA into a cell, but the proteins bound to it affect its regulation. The 3D genome is important.
What is an ideogram?
This allows the individual pattern of each chromosome, to be represented. Chromosomes have some common structural features such as: a centromere between the two arm, a telomere at either end, a short arm called the p (petite) arm and a long arm called the q arm. The gisema staining leaves a recognisable pattern of bands of numbered light and dark bands.
What do the band numbers in ideograms represent?
The bands themselves are caused by differently staining and originally identified with low level of resolution. Only a few bands were visible per chromosome (e.g. 1p, 2p, 3p). Improved technology has allowed more bands to become visible. These newly visible bands have been categorised as sub-bands (e.g. 1p11, 2p21, 3p22). Further technological improvements have allowed sub-sub-bands (e.g. 1p11.1, 3p21.1). Improved resolution helps identify smaller aberrations.
Define bands per haploid set (bphs)?
This identifies the improvement of the level of detail that can be seen on a chromosome, the higher the bphs, the more detail that can be seen. It is important to remember that bands do not represent genes or families of genes, but simply different areas of compaction:
•Dark (heterochromatin) more compact fewer genes
•Light (euchromatin) more open more genes
Define aneuploidy
This describes an abnormal number of chromosomes. This causes problems, as the genome has developed such that having 2 copies of the chromosome is sufficient.
What is meiosis?
This is a special form of the cell cycle used to produce gametes and ensure their genetic variation. Meiosis enables random assortment of homologues and recombination. The purpose of meiosis is fundamentally the reduction from diploid (2n=46) to haploid (n=23).
What is non-disjunction?
This occurs when the process of meiosis goes wrong. Non-disjuncture results in uneven number of chromosomes in daughter cells and can occur in either meiosis I or meiosis II. If it occurs in meiosis I, then all the daughter cells are affected. But, if it occurs in meiosis I, then half of the daughter cells are affected. This means that it always results in either +1 (trisomy) or -1 (monosomy) chromosome.
Outline sex chromosome aneuploidy
Most common form of chromosomal abnormality, affecting 1 in 400 males and 1 in 650 females. The sex chromosome imbalance is tolerated because of:
> X-inactivation of excess X chromosome, meaning only one X-chromosome is active
> Low gene content of Y chromosome
When inactivated the abnormal number X-chromosome can have effect, if both the X and Y chromosome have a PAR (pseudo-autosomal region), as this region is not inactivated with the rest of the chromosome.
What is the second most common aneuploidy?
This is trisomy 21, more common known as Down’s syndrome. It has this name due to the 3 copies of chromosome 21. Most cases of trisomy 21 arise due to non-disjunction during maternal meiosis.
How does age effect the risk of maternal non-disjunction?
Although the risk of Down’s syndrome increases significantly with the mothers age, 75% of children with Down’s syndrome are born to mothers under the age of 35. However, this may simply be due to the fact that 90% of all children are born to mothers under the age of 35.
Why does maternal age increase risk of aneuploidy?
This is due to inherent vulnerability of oogenesis. Paused in utero in prophase I until puberty, secondary oocyte arrests in metaphase II. Only competes if fertilized. One primary oocyte yields only one ovum, but there is a finite number of primary oocytes. In older mothers, the ovum would’ve been stuck in one stage or the other of meiosis, for decades, leading to the degradation of factors which hold homologous chromatids together.
Outline the vulnerability of male meiosis
Males have no equivalent to oocyte mitotic arrest. Their primary spermatocytes undergo ~23 mitotic divisions per year and potentially accumulate defects. Paternal Age not risk factor increased aneuploidy, but does affect a subset of single gene disorders, caused by point mutations in FGFR2, FGFR3 and RET, including:
1) Apert syndrome
2) Crouzon syndrome
3) Pfeiffer syndrome
These syndromes are thought to be enhanced by ‘selfish spermatogonial selection’ resulting from a selective advantage over neighbouring wild type cells.
What is a risk factor in paternal aneuploidy not found in maternal?
Although age does not have any effect on paternal aneuploidy, smoking has been found to be a risk factor, not associated with maternal aneuploidy.
What is the pregnancy risk of aneuploidy?
Aneuploidy causes 5% still births and 50% of spontaneous abortions.
It also effect 5% of all clinically recognized pregnancies. Trisomy of all chromosomes has been detected prenatally and can lead to miscarriages, as most are trisomies are not compatible with life. Monosomy is also very poorly tolerated. Aneuploidy is estimated 50% preimplantation embryos.
What is chromosomal cross over?
This occurs in prophase I and increases genetic diversity. The pairs of chromosomes align and chiasma form, allowing crossover to occur. This is a common process that occurs 1-3 times per chromosome per meiosis. Crossover can occur from a single point, so large portion of terminals of chromosomes are swapped, or it can it can occur within the middle of the chromosomal material in a double cross over., meaning portions in the centre of the chromosomes are swapped over. However it can sometimes go very wrong.
What is unequal crossover?
This is an abnormality that occurs during crossing over when pairs of chromosomes are aligned incorrectly. This results in daughter chromosomes receiving unequal material, one receiving extra material, and one having a deletion of its material.
What are the homologous chromosome abnormalities associated with unequal crossing over?
1) Deletion: Can be the result of unequal cross over. Breaks in chromosome. Can occur at ends.
2) Duplication: Most often caused by unequal cross over, genetic material is duplicated during cross over.
3) Paracentric inversion: Carriers often unaffected. Estimated to occur in 1 in 1000 people. Can cause reproductive problems. Children with deletions/insertions.
What are the non-homologous chromosome abnormalities associated with unequal crossing over?
If the train of material between non-homologous chromosomes occurs in a uni-directional manner, then insertion can occur. The mutual exchange of material can also occur, when translocation of material leads to each of the derivative chromosomes having parts of the other chromosome on them. If this occurs in a balanced manner, it does not affect the carrier, but may cause problems in off spring - such as partial trisomy or monosomy (e.g. Cri-du-chat syndrome). Can occur in Somatic cells cf Philadelphia chromosome t(9;22)(q34;q11) CML.
Outline inherited chromosomal abnormalities
Many chromosomal abnormalities are de-novo. Some people are unidentified carriers as they are unaffected by their translocation of genetic material for instance. However, during gametogenesis, the homologous chromosomes could be partitioned in different ways to produce either normal, balanced translocation carrier or unbalanced offspring. The unbalanced offspring would be affected by the abnormality.
Outline chromosomal deletions
These are classified into two forms:
1) Microscopic – be detected easily in microscope
> Cri-du-chat syndrome 46,XY, deletion of short arm (p) of chromosome 5
2) Microdeletion - seen in high resolution banding; molecular genetics
> Despite name still 20+ genes deleted
> Velocardiofacial/DiGeorge syndrome 22q11.2 del
