Introduction To Genetics

Question 1

What makes up the human genome?

Answer 1

Complete (haploid) set of genetic material in an organism that contains 23 pairs of chromosomes:

• 22 pairs of autosomes
• 1 pair of sex chromosomes (XX = female, XY = male)

Question 2

What makes up our genotype?

Answer 2

Genes, which are segments of DNA, within the genome encode RNA and usually protein

Question 3

What is the central dogma of molecular biology?

Answer 3

DNA encodes mRNA which encodes protein

Question 4

What is phenotype?

Answer 4

Anatomy, physiology and psychology which is influenced by our genotype and the environment so it can change over time

Question 5

What is a monogenetic disease? How do you investigate it?

Answer 5

Single gene abnormality e.g. cystic fibrosis - investigate with molecular genetic tests e.g. PCR

Question 6

What is a multifactorial/polygenetic disease? How do you investigate it?

Answer 6

Multiple genes and environmental influences are involved e.g. heart disease - assess RISK with molecular genetic tests e.g. PCR

Question 7

What ii a chromosomal disease? How do you investigate it?

Answer 7

Abnormality of chromosome structure or number e.g. down syndrome - investigate by cytogenetics e.g. karyotype

Question 8

Are all genetic diseases inherited?

Answer 8

No as new mutations can occur

Question 9

What is a genetic polymorphism?

Answer 9

If different versions of a gene exist in a population, the gene is polymorphic - different versions are called ALLELES with the most common one in the population (usually not ass. with disease) is the wild-type

Question 10

What is the difference between homozygous and heterozygous chromosomes?

Answer 10

Homo: 2 alleles over both the chromosome pairs are identical

Hetero: 2 alleles over both the chromosomes pairs are different or unmatched

Question 11

What is the difference between dominant and recessive alleles?

Answer 11

Dominant alleles determine phenotype in heterozygous individuals

Recessive alleles only determine phenotype if they are present in as a homozygous pair - if an individual is heterozygous, they are a ‘carrier’

Question 12

What is a punnet square?

Answer 12

Simple grid used to draw the expected outcomes of matings which can be used to predict the probably that a new individual will have a particular genotype

Question 13

How are punnet squares drawn?

Answer 13

• Genotypes of parents are written along top and down the left side of the square
• Dominant alleles are represented by capital letters
• Recessive alleles are represented by the same letter as dominant allele but in lower case
• 4 possible genotypes resulting are added to the grid and % chances of genotypes can be worked out

Question 14

What is Mendel’s law of uniformity?

Answer 14

If homozygous dominant and homozygous recessive individuals are mated, the offspring are identical to one another i.e. there is no blending of dominant and recessive

Question 15

What is Mendel’s law of segregation?

Answer 15

During formation of gametes, the members of each gene pair separate so that each gamete carries only one copy of the gene

Question 16

What is Mendel’s law of independent assortment?

Answer 16

Each gene pair segregates independently of other gene pairs (unless they are EXTREMELY close together)

Question 17

What is autosomal dominant inheritance/vertical pattern of inheritance?

Answer 17

Dominant alleles are expressed and determine phenotype when they are present as a single or duplicate copy so an affected person must have an affected parent (i.e. it does not skip generations) and usually involve a GAIN of function in protein encoded - low frequency if they are ass. with disease e.g. familial hypercholesterolaemia, HD and achondroplasia

Question 18

What is achondroplasia?

Answer 18

Premature differentiation of chrondrocytes at growth plates due to Fibroblast Growth Factor Receptor 3 (FGFR3) causing bone growth abnormality and short stature

Question 19

What is autosomal recessive inheritance?

Answer 19

Recessive alleles are only expressed and determine phenotype when 2 copies are present and usually involve a LOSS of function in protein - heterozygous individuals or ‘carriers’ are healthy and can be common in disease-causing alleles esp. in consanguinity (4% in compared to 2% normally) because there is a higher risk both parents are carriers of the same recessive allele increasing risk of having affected children

Question 20

What is consanguinity?

Answer 20

Sharing of blood and refers to matings where the partners have at least one common ancestor considered back to great-grandparent level i.e. second cousins

Question 21

What is genetic load?

Answer 21

The hidden detrimental component of our genome i.e. the lethal pre-natal mutations and harmful recessive disorders for which we are carriers

Question 22

What is the exception to Mendel’s law of inheritance?

Answer 22

Co-dominance where genes do not have dominant or recessive alleles, but heterozygous individuals have a blend of 2 the phenotypes e.g. A and B blood group encoding A and B surface antigens (O is recessive because it is the absence of either)

Question 23

What is overdominance?

Answer 23

Homozygous dominant individuals have a more severe effect than heterozygotes; often homozygosity is incompatible with life

Question 24

What is incomplete penetrance?

Answer 24

Not all individuals with a disease-causing genotype exhibit the disease clinically

Question 25

What is genomic imprinting?

Answer 25

Alleles have different effects depending on the parent of origin; they may have no effect if inherited from one or the other parent

Question 26

What are sex-linked effects?

Answer 26

Where the gene is on the sex chromosome (XX/XY) so if a gene is on both the X and Y chromosomes it will be inherited identically to autosomal genes - most on X chromosome are recessive whereas Y-linked genes and X-linked dominant are rare with males being more affected by X-linked disease receiving it from carrier mother (50% chance)

Question 27

What are examples of sex-linked recessive diseases?

Answer 27

Most commonly affect males:
Red/green colour blindness
Duchenne muscular dystrophy
Fragile X syndrome
Haemophilia A

Question 28

What is mitochondrial inheritance?

Answer 28

Mitochondria contain DNA which is inherited entirely from the mother

Question 29

What is genetic linkage?

Answer 29

Combinations of genes tend to be inherited together because they are located closely together on one chromosome pair

Question 30

What is dynamic mutation?

Answer 30

Genetic diseases occur with increasing severity in consecutive generations due to expansion of a repetitive DNA sequence

Question 31

What is mosaicism?

Answer 31

When different cells within the same individual have different genotypes usually as a result of an error in DNA replication and chromosome separation in the very early embryo (2-8 cell stage) - if 1 cell line is abnormal (e.g. in Trisomy 21), but the other cell line is normal the abnormal effects may be ameliorated

Question 32

Is mosaicism common?

Answer 32

It is difficult to predict the occurrence or its effects but it may not be uncommon - affected individuals may not even be aware of it until as offspring is born who is clearly affected by disease e.g. if all gametes are affected

Question 33

How do you record a genetic history?

Answer 33

1. When taking a genetic disease history, draw a family pedigree showing who is affected to help determine the mode and risk of inheritance
2. For each individual record name, DOB, date/cause of death and medical conditions
3. Consider consanguinity, miscarriages, terminations of pregnancy, still births and infant deaths

Question 34

When is genetic counselling offered? Why?

Answer 34

In the process of family planning to access the risk to offspring or of late onset disease in adults

Question 35

What symbols are used in pedigrees?

Answer 35

Male = square on L
Female = circle on R
Person of unknown sex/unborn child = diamond

Unaffected = hollow 
Affected = shaded 
Carrier = half-shaded
Deceased = slash 
Person of unknown genetic status = question mark 

Marriages/matings = horizontal lines
Children = vertical line and then on a horizontal line in BIRTH ORDER from L to R