Inheritance Lecture Note

INHERITANCE SEXUAL LIFE CYCLE Gametes are sex cells formed by the process of meiosis – males produce sperm and the females produce ova. The gametes are haploid, meaning they only possess one copy of each chromosome. When egg and sperm fuse during fer-lisa-on, the resul-ng offspring will contain two copies of each chromosome (these cells are classed as diploid). These new diploid cells will be gene-cally unique as they contain chromosomes from two sources. Haploid Cells Diploid Cells FUSION Zygote Egg MITOSIS Sperm MEIOSIS AUTOSOMES In all sexually reproducing organisms, chromosomes will exist as homologous pairs (i.e. a maternal copy and a paternal copy). The homologous pairs will have iden-cal structures (same size, same centromere posi-on, same banding paIerns) and will also carry the same sequence of genes at the same loci posi-ons. However, as the paired chromosomes came from different origins (maternal versus paternal copy), the two alleles at each gene locus may be different. Any chromosome that always exists as a matched pair is called an autosome (i.e. not the sex chromosomes). PAIR 1 PAIR 2 SEX CHROMOSOMES In diploid organisms, sex is determined by a pair of chromosomes called sex chromosomes (heterosomes). Unlike autosomes, sex chromosomes are not homologous and possess different genes. Sex in humans will be determined by the XY system. Males possess an X chromosome and a much shorter Y chromosome (XY), while females possess two copies of the larger X chromosome (XX). The Y chromosome contains the genes responsible for developing the male sex characteris-cs. In its absence, the female sexual characteris-cs will alterna-vely con-nue to develop. Y X GENOTYPE All members of a single species will share iden-cal genes, but individuals may possess different versions of a specific gene-c characteris-c. These alternate forms of a gene are called alleles. Alleles typically differ by only one or a few bases and new alleles can be made via gene mutaEons. The complete set of alleles that a given organism possesses is called the genotype – it reflects the gene-c iden-ty of a par-cular individual. Gene: Eye color Alleles: Different shades (brown, blue, green, etc.) TYPES OF ZYGOSITY For any given gene, the combina-on of alleles (genotype) can be categorised as follows: • • Homozygous: If maternal and paternal alleles are the same, the genotype is said to be homozygous Heterozygous: If maternal and paternal alleles are different, the genotype is said to be heterozygous Males have different sex chromosomes (XY), meaning they have only one allele for each sex-linked gene. When there is only one copy of an allele for a gene, the individual is said to be hemizygous for that gene. Individuals who are hemizygous cannot be carriers of recessive disease condi-ons – this is the reason why X-linked recessive disorders occur more commonly in males. HOMOZYGOUS Alleles are the same HETEROZYGOUS Alleles are different HEMIZYGOUS Only one allele (males) PHENOTYPE Phenotype describes all of the observable characterisEcs of a given organism, and will be influenced by both the genotype and the environment. Unlike the genotype, which represents the gene sequences, the phenotype is a reflec-on of the proteins that are produced. The type of proteins produced by a cell will be determined by the genotype, but the ac-vity or expression of the proteins can be impacted by a variety of environmental factors. For example, produc-on of skin pigment (melanin) is influenced by sun exposure. EPIGENETICS While the genotype is an important factor in determining the physical expression of inheritable characteris-cs (phenotype), it is not the only contribu-ng factor. A phenotype can also be influenced by the paIerns of expression of par-cular genes. Epigene-cs describes differences that are caused by changes in gene expression, rather than by changes within the allele sequence (phenotypic plasEcity). There are various factors that determine whether a given gene is switched on or off: • • • • Diet: Certain foods trigger specific metabolic responses Lifestyle: Gene expression is influenced by ac-vity levels Environment: External condi-ons (UV) can ac-vate genes Pathogens: Diseases result from a loss of homeostasis Nature Sport Disease Diet Epigene'cs can influence phenotype GENETIC CROSSES Gene-c crosses determine the allele combina-ons and phenotypes for poten-al offspring. Gene-c crosses are oeen conducted using plants, as pollen transfer requires external agents that can easily be controlled and this allows breeding to be carefully manipulated. Plants also have the benefit of being able to produce many seeds in short periods of -me. Gene-c crosses can be performed according to the following steps: • • • • Designate poten-al alleles (dominant = capital leIer, recessive = lowercase, codominant = superscript) Write down the genotype and phenotype of the prospec-ve parents (this is the P genera-on) Draw a grid with maternal gametes on the top and paternal gametes on the lee (this is a PunneO grid) Complete the PunneI grid to determine the genotypes and phenotypes of offspring (F1 genera-on) MODES OF INHERITANCE A monogenic trait describes a characteris-c that is encoded by a single gene. The two alleles may interact in different ways to affect the physical expression of the trait (phenotype). The way in which alleles are expressed is called the mode of inheritance. Different paIerns can arise depending on the allele behaviour: • • • • Complete dominance: One allele is expressed (dominant) over another allele (recessive) Codominance: Both alleles are autonomously expressed to create a dual phenotype (both present) Incomplete dominance: Neither allele is completely expressed, resul-ng in a blended phenotype Sex-linkage: The gene is on a sex chromosome and so the inheritance will demonstrate sex bias 1. COMPLETE DOMINANCE Most traits follow a classical dominant / recessive paIern of inheritance, whereby one allele is expressed over the other allele. The dominant allele will mask the recessive allele when in a heterozygous state and the homozygous dominant and heterozygous forms will therefore be phenotypically indis-nguishable (the recessive allele will only ever be able to be expressed within the phenotype when in a homozygous state). When represen-ng alleles, the conven-on is to capitalise the dominant allele and use a lowercase leIer for the recessive allele (same leIer must be used as the alleles are alterna-ve versions of the same gene). • Example: Mouse colour coats – black fur coats (BB or Bb) are dominant to brown fur coats (bb) An example of a gene-c disorder caused by a recessive allele is phenylketonuria. This disorder is caused by a muta-on to the gene that codes for an enzyme needed to convert phenylalanine into tyrosine. The excess phenylalanine is instead converted into phenyl ketone – which builds up to toxic levels within the blood and urine. Untreated PKU can lead to brain damage and mental retarda-on, as well as other serious medical issues. PKU is treated by enforcing a strict diet that restricts the intake of phenylalanine to prevent its build up within the body. This low-protein diet should include certain types of fruits, grains and vegetables, along with precise quan--es of amino acid supplements. Because the condi-on is recessive, both parents must either have the condi-on themselves or be heterozygous carriers in order to pass the disease to offspring. 2. CODOMINANCE Codominance occurs when pairs of alleles are both expressed equally in the phenotype of a heterozygote. Heterozygous individuals therefore have a different phenotype in comparison to homozygous dominant individuals as the alleles are having a joint effect. When represen-ng alleles, the conven-on is to use a common capital leIer with superscripts to represent the different versions of the dominant allele (recessive alleles are s-ll represented with a lowercase leIer). • Example: Human blood groups – IA and IB alleles are codominant, allowing for an AB blood group (IA IB) Fun fact: As the immune system targets foreign markers, O blood is the universal donor type (no markers). 3. INCOMPLETE DOMINANCE Incomplete dominance occurs when two characteris-cs blend together in the phenotype of a heterozygote. An example of incomplete dominance can be seen in the flower colour of Mirabilis jalapa (commonly called the four o’clock flower or the marvel of Peru). When plants with dark pink flowers (CP CP) are crossed with white-flowered plants (CW CW), the offspring will have light pink flowers (CP CW). This reflects the fact that neither allele for flower colour (dark pink or white) is wholly dominant or recessive, so the heterozygous combina-on will produce a blended trait. The lighter coloura-on is caused by the fact that only the allele for a dark pink flower codes for pigment (white flowers produce no pigment), so heterozygotes produce less amounts of pigment overall – leading to the lighter coloura-on. 4. SEX LINKAGE Sex linkage refers to when a gene is found on a sex chromosome (X or Y). Because males and females have different combina-ons of sex chromosomes (males = XY ; females = XX), the paIerns of inheritance will be different according to the sex of the offspring. Sex linkage typically refers to X-linked genes specifically, as the Y chromosome is very short and has very few genes present (< 100). Sex linked alleles are represented as superscripts aIached to the relevant sex chromosome (example: XA or Xa). X-Linked Dominant Traits: • As females possess two X chromosomes, an X-linked dominant trait will be more common in women • An affected father always has affected daughters (daughters must inherit the father’s X chromosome) • Sons only inherit the condi-on if the mother is affected (sons inherit their X chromosome from mother) X-Linked Recessive Traits: • As males only possess one X chromosome, an X-linked recessive trait will be more common in men • This is because males cannot be carriers for X-linked recessive traits (they cannot be heterozygous) • Affected mothers always have affected sons, while unaffected fathers cannot have affected daughters An example of an X-linked recessive disorder is haemophilia. Haemophilia is a gene-c disorder whereby the body’s ability to control blood clomng (and hence stop bleeding) is impaired. The gene responsible for controlling the clomng cascade is located on the X chromosome, meaning it occurs more frequently in males. Females can only develop haemophilia if they possess two recessive alleles (one from each parent), which means that the father must be a haemophiliac for the daughter to be affected. PEDIGREE CHARTS A pedigree is a chart of the gene-c history of a family over several genera-ons. Males are represented as squares (☐), while females are represented as circles (¡). Shaded symbols denote a condi-on of interest. A horizontal line between man and woman represents ma-ng, and all offspring are shown as offshoots. Genera-ons are listed using roman numerals (I, II, III, IV, etc.) and individuals are numbered from eldest to youngest (for example: the youngest of three grandchildren would be labelled as III-3). Certain paIerns in a pedigree chart can be used to iden-fy the mode of inheritance for a given condi-on: • Autosomal dominant: If both parents are affected and any offspring are not, the condi-on must be dominant (unaffected offspring are homozygous recessive and both parents must be heterozygous). • Autosomal recessive: If both parents are unaffected and any offspring are not, the condi-on must be recessive (affected offspring are homozygous recessive and both parents must be heterozygous). It is not possible to conclusively determine sex linkage from pedigree charts, as autosomal traits could poten-ally generate the same results. However certain trends can show that a trait is not sex-linked: • X-linked dominant: If a male is affected, all daughters must be affected. An unaffected mother cannot have an affected son (or an affected father). Traits will tend to occur more frequently in females. • X-linked recessive: If a female is affected, all sons must be affected. An unaffected mother can have affected sons if she is a carrier (heterozygous). Traits will tend to occur more commonly in males. POLYGENIC INHERITANCE Some characteris-cs are determined by the interac-on of mulEple genes (polygenic traits). These traits will consequently exhibit a far greater spectrum of varia-on (i.e. conEnuous variaEon). Traits that exhibit con-nuous varia-on will be normally distributed and include human height, weight and skin coloura-on. Con-nuous varia-on can be represented graphically via box-and-whisker plots. These plots can show the spread of data by iden-fying minimum, maximum and median values. Outliers can be iden-fied as falling outside the first or third quar-les by a value of more than 1.5 -mes the interquar-le range (IQR). Minimum Min == 11 1 1 2 2 3 4 5 6 7 7 8 9 9 9 Maximum Max = 9 = 9 Median = 5.5 Q1 = 2Q1 =Median = 5.5 2 Q3 = 8Q3 = 8 IQR = 8 – 2 = 6 Outliers = Q1 – ( 1.5 × IQR ) = < –7 Minimum Outlier = 2 – (1.5 × 6) = less than –7 1 2 3 4 5 6 7 8 9 Outliers = Q3 + Outlier ( 1.5 × IQR > 17× 6) = more than 17 Maximum = 8 )+=(1.5