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FRIEDHELM HILDEBRANDT AND HEYMUT OMRAN
values between 0 and 0.5 will be observed, depending on the distance between the two loci. Therefore, the recombination fraction is related to the
genetic distance x between two gene loci. This relation is given by a so-called
map function, the simplest of which is the function by Morgan: x=.The
genetic distance x is measured in cM (centiMorgans), where lcM 1% recombination.
The likelihood method: the LOD score
Since recombination is a stochastic event, a statistical test has to be performed when interpreting observed recombinations. The likelihood method is used to calculate such a statistical parameter which is called the LOD
score:
The likelihood L(8) that there is linkage between two loci of
unknown distance is calculated for recombination fractions 8. Theta is
varied between 8=0 (complete linkage) and 8=0.5 (no linkage). The likelihood of linkage at a certain recombination fraction ( equivalent to
Fig. 7. "LODVIEW", an evaluation programm for total genome linkage analysis. LODIN5,
the LODVIEW input file for human Chromosome 5. LOD score data were entered into
the preformatted file LODIN5. Row 1 contains the following data: in cells B1 toLl the names
offamilies 1 - 11, which generate the labels "fam 1 - fam 11" in the legend to Figure 8; in cells
M1 to 01 the labels for 2-point LOD scores generating the labels "curve M, N, 0" in the legend
to Figure 8; in cell P1 the label for multipoint LOD scores generating the label "multipoint" in
the legend of Figure 8. Each row from row 2 on represents an interval of 5 cM(K) on the
abscissa in Figure 8, starting at 5pter (row 2) and ending at 5qter (row 37).
Rows 2 - 37 contain the following data: In column A a row will contain MS marker information if this marker is mapped to the respective 5 cM(K) interval. MS markers are positioned
relative to their approximate location within the 5 cM(K) grid. Markerinformation is given in
the following order: symbol, name, (location) heterozygosity index. Following this information, the genetic distance to the next MS-PCR-marker to the right is given in cM(K). If no
marker is known for an interval, cumulative map distances in cM(K) are given at every
10 cM(K) intervals.
Thus, column A generates the labels appearing above the abscissa in Figure 8. Columns B to L
contain LOD scores at a recombination fraction of 8 = 0.05 which are represented in Figure 8
as histograms segmented by family. Columns M to 0 contain LOD scores calculated at 8 =
4.98, 9.87, 14.57, 19.00, etc., yielding LOD score curves surrounding each marker in Figure 8 at
genetic distances of xK = 5, 10, 15, 20 cM(K) etc., respectively. Column P contains LOD scores
calculated for 3-point linkage between each of two adjacent markers and a disease locus calculated with the program LINKMAP as taken from the outputprogram LRP of the LINKAGE
package. The results are displayed as multipoint curves in Figure 8. All cells in the table are
preformatted in order to automatically produce the graphical representation of data shown in
Figure 8.
FRIEDHELM HILDEBRANDT AND HEYMUT OMRAN
values between 0 and 0.5 will be observed, depending on the distance between the two loci. Therefore, the recombination fraction is related to the
genetic distance x between two gene loci. This relation is given by a so-called
map function, the simplest of which is the function by Morgan: x=.The
genetic distance x is measured in cM (centiMorgans), where lcM 1% recombination.
The likelihood method: the LOD score
Since recombination is a stochastic event, a statistical test has to be performed when interpreting observed recombinations. The likelihood method is used to calculate such a statistical parameter which is called the LOD
score:
The likelihood L(8) that there is linkage between two loci of
unknown distance is calculated for recombination fractions 8. Theta is
varied between 8=0 (complete linkage) and 8=0.5 (no linkage). The likelihood of linkage at a certain recombination fraction ( equivalent to
Fig. 7. "LODVIEW", an evaluation programm for total genome linkage analysis. LODIN5,
the LODVIEW input file for human Chromosome 5. LOD score data were entered into
the preformatted file LODIN5. Row 1 contains the following data: in cells B1 toLl the names
offamilies 1 - 11, which generate the labels "fam 1 - fam 11" in the legend to Figure 8; in cells
M1 to 01 the labels for 2-point LOD scores generating the labels "curve M, N, 0" in the legend
to Figure 8; in cell P1 the label for multipoint LOD scores generating the label "multipoint" in
the legend of Figure 8. Each row from row 2 on represents an interval of 5 cM(K) on the
abscissa in Figure 8, starting at 5pter (row 2) and ending at 5qter (row 37).
Rows 2 - 37 contain the following data: In column A a row will contain MS marker information if this marker is mapped to the respective 5 cM(K) interval. MS markers are positioned
relative to their approximate location within the 5 cM(K) grid. Markerinformation is given in
the following order: symbol, name, (location) heterozygosity index. Following this information, the genetic distance to the next MS-PCR-marker to the right is given in cM(K). If no
marker is known for an interval, cumulative map distances in cM(K) are given at every
10 cM(K) intervals.
Thus, column A generates the labels appearing above the abscissa in Figure 8. Columns B to L
contain LOD scores at a recombination fraction of 8 = 0.05 which are represented in Figure 8
as histograms segmented by family. Columns M to 0 contain LOD scores calculated at 8 =
4.98, 9.87, 14.57, 19.00, etc., yielding LOD score curves surrounding each marker in Figure 8 at
genetic distances of xK = 5, 10, 15, 20 cM(K) etc., respectively. Column P contains LOD scores
calculated for 3-point linkage between each of two adjacent markers and a disease locus calculated with the program LINKMAP as taken from the outputprogram LRP of the LINKAGE
package. The results are displayed as multipoint curves in Figure 8. All cells in the table are
preformatted in order to automatically produce the graphical representation of data shown in
Figure 8.